KR20180073489A - Novel Pseudomonas aeruginosa specific bacteriophage PA4 and antibacterial composition comprising the same - Google Patents

Novel Pseudomonas aeruginosa specific bacteriophage PA4 and antibacterial composition comprising the same Download PDF

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KR20180073489A
KR20180073489A KR1020170176309A KR20170176309A KR20180073489A KR 20180073489 A KR20180073489 A KR 20180073489A KR 1020170176309 A KR1020170176309 A KR 1020170176309A KR 20170176309 A KR20170176309 A KR 20170176309A KR 20180073489 A KR20180073489 A KR 20180073489A
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pseudomonas aeruginosa
present
aeruginosa
antibiotic
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연영은
김영주
이종석
한범구
김현일
박철세
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Abstract

The present invention relates to a novel bacteriophage PA4 having a killing ability specific to Pseudomonas aeruginosa, particularly carbapenem-based antibiotic resistant Pseudomonas aeruginosa; a pharmaceutical composition, an antibiotic composition, a feed additive composition, a feed, a disinfectant or a washing agent for preventing or treating infectious diseases caused by Pseudomonas aeruginosa, which all include the bacteriophage; and a method for preventing or treating infectious diseases caused by Pseudomonas aeruginosa, which includes a step of administrating the bacteriophage to an object. The method for preventing or treating infectious diseases caused by Pseudomonas aeruginosa using the bacteriophage PA4 has very high specificity to Pseudomonas aeruginosa, and particularly to carbapenem resistant Pseudomonas aeruginosa compared to a conventional chemical material such as antibiotics or the like, and the bacteriophage PA4 is infected to Pseudomonas aeruginosa, thereby having excellent bacteriolytic activity and being strong to physiochemical stimulation. In addition, the bacteriophage PA4 of the present invention is not infected to a host other than bacteria except a human, an animal, a plant, or the like, and thus it is possible to solve a problem of antibiotic resistant bacteria due to abuse of antibiotics, a problem of residual antibiotics in food, and a problem of a wide range of host ranges. Accordingly, the bacteriophage PA4 of the present invention can be variously used in the fields of prevention or treatment of infectious diseases caused by pathogenic Escherichia coli, antibiotic compositions, feed additive compositions, feeds, disinfectants, or washing agents.

Description

신규한 녹농균 특이 박테리오파지 PA4 및 이를 포함하는 항균 조성물{Novel Pseudomonas aeruginosa specific bacteriophage PA4 and antibacterial composition comprising the same}[0001] The present invention relates to a novel P. aeruginosa specific bacteriophage PA4 and an antibacterial composition comprising the same,

본 발명은 녹농균(Pseudomonas aeruginosa), 특히 카르바페넴(carbapenem)계 항생제 내성 녹농균에 특이적인 사멸능을 갖는 신규 박테리오파지 PA4, 상기 박테리오파지를 포함하는 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제 또는 세척제 및 상기 박테리오파지를 개체에 투여하는 단계를 포함하는 녹농균에 의한 감염성 질병의 예방 또는 치료 방법에 관한 것이다.The present invention relates to a novel bacteriophage PA4 having an ability to kill pseudomonas aeruginosa , particularly carbapenem antibiotic-resistant Pseudomonas aeruginosa, an antibiotic composition comprising the bacteriophage, a composition for feed addition, a feed, a disinfectant or a detergent And a method for preventing or treating an infectious disease caused by Pseudomonas aeruginosa including the step of administering the bacteriophage to an individual.

일반적으로 녹농균(Pseudomonas aeruginosa)은 그람 음성균이며, 흔한 감염성 병원균으로서, 항생제에 대한 감수성이 낮아 자연적으로 쉽게 항균제 내성을 획득할 수 있다고 알려져 있다. 다양한 항생제에 내성을 가지는 내성균은 치료가 어려우며, 진행성의 질환을 가진 경우 사망률이 높다. 그나마 베타락탐계 항생제에 대하여 상대적으로 낮은 내성률을 가지고 있어 녹농균 치료 시 다양한 베타락탐계 항생제가 사용되고 있다.In general, Pseudomonas aeruginosa is a gram-negative bacterium, and it is known that it is a common infectious pathogen and has low susceptibility to antibiotics and can easily obtain antimicrobial resistance naturally. Resistant organisms resistant to various antibiotics are difficult to treat, and those with progressive diseases have high mortality rates. In addition, various beta-lactam antibiotics have been used in the treatment of pseudomonas aeruginosa because they have a relatively low resistance to beta-lactam antibiotics.

다만 최근에 베타락탐계 항생제 중에서도 일부 항생제, 특히 카르바페넴에 내성을 나타내는 녹농균이 발견되고 있는 실정인 바, 임상에서 카르바페넴 내성 녹농균의 사멸의 중요성은 크다고 할 수 있다. 구체적으로 항생제에 내성을 가진 녹농균은 전세계적으로 증가하는 추세이고 종합 병원급에서의 카르바페넴 내성률은 29%(2006년)로 보고된바 있고, 특히 국내에서 2008년 6월부터 2009년 7월 동안 중환자실 병원감염감시 결과 카르바페넴 내성률은 68.9%인 것으로 보고되었는 바, 카르바페넴에 대한 녹농균의 내성률이 점점 증가하고 있음을 알 수 있다. 상기 녹농균에 의하여 피부감염, 각막염, 중이염, 폐렴, 균혈증, 패혈증, 수막염과 뇌종양 등이 유발되고 주요 병원감염 원인으로 흔히 요로감염과 인공호흡기관련 폐렴 등이 발생되고 있다. 또한, 녹농균은 인공호흡기를 사용하는 호흡기계 감염, 화상 감염, 낭포성 섬유증 환자의 폐렴을 유발하며, 인공환기기, 흡입카테터, 고여 있는 오염된 물 등의 감염소에 존재하다가 환자에게 직간접적으로 전파되어 정착하게 되는데 진행성의 질환을 가진 환자의 경우에는 치료가 어려워 높은 사망률을 보이는 것으로 알려져 있다.However, recently, some antibiotics, especially carbapenem-resistant P. aeruginosa have been found among beta-lactam antibiotics. Therefore, the clinical significance of carbapenem-resistant P. aeruginosa infection is high. Specifically, P. aeruginosa resistant to antibiotics is increasing worldwide, and the rate of carbapenem resistance in general hospital classes is reported to be 29% (2006). In particular, in Korea from June 2008 to July 2009 Carbapenem resistance rate was reported to be 68.9% as a result of intensive care unit hospital infection monitoring, indicating that the resistance rate of P. aeruginosa to carbapenem is increasing. Pseudomonas aeruginosa causes skin infections, keratitis, otitis media, pneumonia, bacteremia, sepsis, meningitis and brain tumor, and causes of urinary tract infections and pneumonia related to respiratory tract are the main causes of hospital infection. Pseudomonas aeruginosa induces respiratory tract infections, burn infections, and pneumonia in patients with cystic fibrosis using artificial respiration. They are present in infected areas such as artificial ring devices, suction catheters, and contaminated water, It is known that patients with progressive disease have high mortality due to difficulty in treatment.

한편, 박테리오파지(bacteriophage)는 특정 세균을 감염시켜 감염된 세균의 성장을 억제하고 저해하는 세균 특이적 바이러스를 의미한다. 박테리오파지는 박테리아에 감염(infection)한 후 박테리아 세포 내부에서 증식을 하고, 증식 후 자손 박테리오파지들이 박테리아 밖으로 나올 때 숙주인 박테리아의 세포벽을 파괴하는 방식으로 박테리아를 사멸시키는 능력을 갖고 있다. 박테리오파지의 박테리아 감염 방식은 매우 특이성이 높아서 특정 박테리아에 감염할 수 있는 박테리오파지의 종류는 일부로 한정된다. 즉, 특정 박테리오파지는 특정 범주의 박테리아에만 감염할 수 있고 이로 인하여 특정 박테리오파지는 특정 박테리아만을 사멸시키며 다른 박테리아에는 영향을 주지 않는다. 따라서 최근 세균성 질환의 대처 방안으로 박테리오파지(bacteriophage)의 활용이 크게 주목을 받고 있다. 특히 2000년 이후에 항생제 내성균의 증가로 인하여 기존 항생제의 한계성이 나타나고, 기존 항생제의 대체 물질로의 개발 가능성이 부각되면서 다시 박테리오파지가 항-박테리아제로 주목을 받고 있다.On the other hand, bacteriophage refers to a bacterium-specific virus that infects a specific bacterium to inhibit and inhibit the growth of the infected bacterium. Bacteriophages have the ability to kill bacteria by infecting bacteria, multiplying inside bacterial cells, and destroying the cell walls of the host bacteria when the progeny bacteriophages come out of the bacteria after proliferation. The bacteriophage infection method of bacteriophage is highly specific, so the type of bacteriophage that can infect a specific bacterium is limited to some. That is, certain bacteriophages can infect only a specific category of bacteria, which causes certain bacteriophages to kill only certain bacteria and not other bacteria. Recently, the use of bacteriophage has attracted much attention as a countermeasure against bacterial diseases. Especially, since 2000, the limit of existing antibiotics has appeared due to the increase of antibiotic resistant bacteria, and bacteriophage is attracting attention as an anti - bacterial agent again with the possibility of development as a substitute for existing antibiotics.

현재까지 녹농균, 특히 카르바페넴 항생제 내성 녹농균에 의한 감염증을 예방 또는 치료하기 위한 신규한 박테리오파지에 대한 연구는 여전히 부족한 실정이다. 따라서 녹농균, 특히 카르바페넴계 항생제 내성 녹농균에 특이적인 용균활성을 갖는 박테리오파지 및 이의 응용에 대한 기술 개발이 필요하다.To date, research on novel bacteriophages for the prevention or treatment of infections caused by P. aeruginosa, especially carbapenem antibiotic resistant P. aeruginosa, is still lacking. Therefore, it is necessary to develop a technique for bacteriophage having a lytic activity specific to P. aeruginosa, especially carbapenem antibiotic resistant P. aeruginosa, and its application.

한국공개특허 제10-2015-0123396호Korean Patent Publication No. 10-2015-0123396

이에 본 발명자들은 녹농균에 특이적인 용균활성을 갖는 박테리오파지를 분리하고 분리된 박테리오파지의 형태적 및 유전적 특성을 분석하여 상기 박테리오파지가 녹농균, 특히 카르바페넴계 항생제 내성 녹농균을 선택적으로 사멸시킬 수 있음을 확인함으로써 본 발명을 완성하였다.Accordingly, the present inventors have isolated bacteriophage having a lytic activity specific to P. aeruginosa and analyzed the morphological and genetic characteristics of the isolated bacteriophage to confirm that the bacteriophage can selectively kill P. aeruginosa, especially carbapenem antibiotic resistant P. aeruginosa Thereby completing the present invention.

본 발명의 목적은 녹농균에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 PA4를 제공하는 것이다.An object of the present invention is to provide a bacteriophage PA4 comprising the nucleotide sequence shown in SEQ ID NO: 1, which has a killing activity specific to P. aeruginosa.

본 발명의 또 다른 목적은 상기 박테리오파지 PA4를 포함하는, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제 또는 세척제를 제공하는 것이다.It is still another object of the present invention to provide an antibiotic composition, a composition for feed addition, a feed, a disinfectant, or a detergent comprising the bacteriophage PA4.

본 발명의 또 다른 목적은 상기 박테리오파지 PA4를 개체에 투여하는 단계를 포함하는, 녹농균에 의한 감염성 질병의 예방 또는 치료 방법을 제공하는 것이다.It is still another object of the present invention to provide a method for preventing or treating an infectious disease caused by P. aeruginosa, comprising the step of administering the bacteriophage PA4 to an individual.

상기 목적을 달성하기 위하여, 본 발명은 녹농균에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 PA4를 제공한다.In order to achieve the above object, the present invention provides bacteriophage PA4 comprising the nucleotide sequence shown in SEQ ID NO: 1, which has a killing activity specific to P. aeruginosa.

또한, 본 발명은 상기 박테리오파지 PA4를 포함하는, 항생용 조성물을 제공한다.In addition, the present invention provides an antibiotic composition comprising the bacteriophage PA4.

또한, 본 발명은 상기 박테리오파지 PA4를 포함하는, 사료 첨가용 조성물을 제공한다.The present invention also provides a composition for feed addition comprising the bacteriophage PA4.

또한, 본 발명은 상기 사료 첨가용 조성물을 포함하는, 사료를 제공한다.In addition, the present invention provides a feed comprising the feed composition.

또한, 본 발명은 상기 박테리오파지 PA4를 포함하는, 소독제를 제공한다.The present invention also provides a disinfecting agent comprising the bacteriophage PA4.

또한, 본 발명은 상기 박테리오파지 PA4를 포함하는, 세척제를 제공한다.The present invention also provides a detergent comprising the bacteriophage PA4.

또한, 본 발명은 상기 박테리오파지 PA4를 인간을 제외한 개체에 투여하는 단계를 포함하는, 녹농균에 의한 감염성 질병의 예방 또는 치료 방법을 제공한다.In addition, the present invention provides a method for preventing or treating infectious diseases caused by P. aeruginosa, comprising the step of administering the bacteriophage PA4 to an individual other than a human.

본 발명의 박테리오파지 PA4를 이용한 녹농균에 의한 감염성 질병의 예방 또는 치료 방법은 기존의 항생제 등의 화학물질에 비해 녹농균, 특히 카르바페넴 내성 녹농균에 대한 특이성이 매우 높고, 상기 박테리오파지 PA4는 녹농균에 감염하여 탁월한 용균 활성을 나타내고 물리화학적 자극에 강하다는 장점을 가지고 있다. 또한 본 발명의 박테리오파지 PA4는 사람, 동물, 식물 등 세균 외의 다른 숙주에는 감염되지 않으므로, 항생제의 오남용으로 인한 항생제 내성균의 문제점, 식품 내의 항생제의 잔류 문제, 광범위한 숙주범위의 문제점을 해결할 수 있는 장점이 있다. 따라서, 본 발명의 박테리오파지 PA4는 녹농균에 의한 감염성 질병의 예방 또는 치료, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제, 또는 세척제 분야에서 다양하게 사용될 수 있다.The method for preventing or treating infectious diseases caused by P. aeruginosa using the bacteriophage PA4 of the present invention is highly specific for P. aeruginosa, especially carbapenem-resistant P. aeruginosa, compared to conventional antibiotics and other chemicals, and the bacteriophage PA4 is infected with P. aeruginosa It exhibits excellent lytic activity and is strong against physicochemical stimuli. In addition, the bacteriophage PA4 of the present invention is not infected with any host other than bacteria such as human, animal, and plant. Therefore, it is possible to solve problems of antibiotic resistant bacteria caused by abuse of antibiotics, residual antibiotics in food, have. Therefore, the bacteriophage PA4 of the present invention can be used variously in the field of prevention or treatment of infectious diseases caused by P. aeruginosa, compositions for antibiosis, composition for feed addition, feed, disinfectant, or detergent.

도 1은 하수에서 채취한 시료 내 박테리오파지 PA4의 존재를 확인한 결과를 나타낸 도이다.
도 2은 박테리오파지 PA4의 녹농균에 대한 용균반 형성 활성을 확인한 결과를 나타낸 도이다.
도 3은 박테리오파지 PA4의 유전자 맵을 나타낸 도이다.
도 4는 전자 현미경을 통해 박테리오파지 PA4의 형태학적 특성을 확인한 결과를 나타낸 도이다.
도 5는 박테리오파지 PA4의 단백질 패턴을 SDS-PAGE를 통해 확인한 결과를 나타낸 도이다.
도 6은 박테리오파지 PA4의 pH 안정성을 확인한 결과를 나타낸 도이다.
도 7은 박테리오파지 PA4의 온도 안정성을 확인한 결과를 나타낸 도이다.1 is a view showing the result of confirming the presence of bacteriophage PA4 in a sample collected from sewage.
Fig. 2 is a graph showing the result of confirming the activity of the bacteriophage PA4 to form pseudomonas sp.
3 is a diagram showing a gene map of bacteriophage PA4.
FIG. 4 is a graph showing the morphological characteristics of bacteriophage PA4 through an electron microscope.
FIG. 5 shows the result of SDS-PAGE analysis of the protein pattern of bacteriophage PA4.
6 is a graph showing the result of confirming the pH stability of bacteriophage PA4.
7 is a graph showing the result of confirming the temperature stability of the bacteriophage PA4.

이하, 본 발명에 대해 상세히 설명한다.Hereinafter, the present invention will be described in detail.

본 발명은 녹농균에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 PA4를 제공한다.The present invention provides a bacteriophage PA4 comprising the nucleotide sequence of SEQ ID NO: 1, which has a killing activity specific to P. aeruginosa.

본 발명에서, 용어 박테리오파지(bacteriophage)는 특정 세균에 감염하여 당해 세균의 성장을 억제하고 저해하는 세균 특이적 바이러스로, 단일 혹은 이중 사슬의 DNA 또는 RNA를 유전 물질로 포함하는 바이러스를 의미한다.In the present invention, the term bacteriophage refers to a bacterium-specific virus that infects a specific bacterium and inhibits and inhibits the growth of the bacterium, and includes a single or double-stranded DNA or RNA as a genetic material.

본 발명의 박테리오파지 PA4는 녹농균, 특히 카르바페넴 내성 녹농균에 대해 용균활성이 탁월하다. 상기 박테리오파지 PA4는 130-150nm의 크기로, 정이십면체의 머리를 가지며 수축성 꼬리가 있는 마이오비리대(Myoviridae)에 속한다. 본 발명의 박테리오파지 PA4는 단백질 패턴 분석 결과 90 kDa, 60 kDa, 43 kDa, 23 kDa 그리고 16 kDa의 단백질을 포함함을 확인하였다. 그 전체 염기서열을 서열번호 1로 표시하였다. 또한 상기 박테리오파지 PA4는 pH 및 온도에 대한 안정성이 우수한 특성을 가지고 있다.The bacteriophage PA4 of the present invention has excellent lytic activity against P. aeruginosa, particularly carbapenem-resistant P. aeruginosa. The bacteriophage PA4 is 130-150 nm in size and belongs to Myoviridae, which has a head with a regular twenty-sided body and a contractile tail. The protein pattern analysis of the bacteriophage PA4 of the present invention confirmed that it contained proteins of 90 kDa, 60 kDa, 43 kDa, 23 kDa and 16 kDa. The entire nucleotide sequence thereof is shown in SEQ ID NO: 1. In addition, the bacteriophage PA4 has excellent stability against pH and temperature.

박테리오파지 PA4는 서열번호 1로 표시되는 염기서열을 전체 유전자의 전체 또는 일부로서 포함할 수 있다. 또한, 본 발명의 박테리오파지 PA4는 서열번호 1로 표시되는 염기서열, 및 상기 염기서열의 기능적 동등물로 이루어질 수 있다. 상기 기능적 동등물이란 염기서열의 변형, 치환의 결과, 상기 서열번호 1로 표시되는 염기서열과 적어도 70% 이상, 바람직하게는 80% 이상, 더욱 바람직하게는 90% 이상, 더더욱 바람직하게는 95% 이상의 서열 상동성을 갖는 것으로, 서열번호 1로 표시되는 염기서열과 실질적으로 동질의 생리활성을 나타내는 서열을 의미한다.Bacteriophage PA4 may contain the nucleotide sequence shown in SEQ ID NO: 1 as whole or part of the entire gene. In addition, the bacteriophage PA4 of the present invention may comprise the nucleotide sequence shown in SEQ ID NO: 1 and the functional equivalent of the nucleotide sequence. The functional equivalent means at least 70% or more, preferably 80% or more, more preferably 90% or more, still more preferably 95% or more of the nucleotide sequence shown in SEQ ID NO: 1 as a result of modification or substitution of the nucleotide sequence. Or more and having substantially the same physiological activity as the nucleotide sequence shown in SEQ ID NO: 1.

상기와 같은 녹농균 특이적 용균활성, 내산성, 내염기성 및 내열성은 본 발명의 박테리오파지 PA4를 녹농균에 의한 감염성 질병의 예방 및 치료용 조성물, 및 상기 박테리오파지 PA4를 유효성분으로 포함하는 다양한 제품에 적용함에 있어, 다양한 pH 범위의 적용이 가능하게 한다.In the application of the bacteriophage PA4 of the present invention to a composition for the prevention and treatment of infectious diseases caused by Pseudomonas aeruginosa and to various products containing the bacteriophage PA4 as an active ingredient, such as pseudomonas aeruginosa activity, acid- , Making it possible to apply various pH ranges.

본 발명의 박테리오파지 PA4는 하수처리장, 도계장 및 양계농장 부근의 하수로부터 시료를 채취하여 분리한 박테리오파지로서, 본 발명자는 이를 박테리오파지 PA4로 명명하고 2016년 10월 21일에 한국미생물보존센터에 수탁번호 KFCC11697P로 기탁하였다. The bacteriophage PA4 of the present invention is a bacteriophage obtained by collecting samples from sewage treatment plants, sowing fields and poultry farms and isolating them as bacteriophage PA4. On October 21, 2016, the bacteriophage PA4 was deposited with the Korean Microorganism Conservation Center under accession number KFCC11697P ≪ / RTI >

또한, 본 발명은 상기 박테리오파지 PA4를 포함하는, 녹농균에 의한 감염성 질병의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention also provides a pharmaceutical composition for preventing or treating an infectious disease caused by P. aeruginosa comprising the bacteriophage PA4.

본 발명에서, 상기 녹농균은 항생제 내성 녹농균일 수 있으며, 바람직하게는 베타락탐계 항생제 내성 녹농균일 수 있고, 보다 바람직하게는 카르바페넴계 항생제 내성 녹농균이나, 이에 본 발명이 제한되는 것은 아니다. 임상적 측면에서 카르바페넴계 항생제는 페니실린(penicillin)의 골격과 유사하기 때문에 β-락탐환(環)과 5원환(5員環)이 있지만 5원환의 S(황)원자가 C(탄소)원자와 치환하고, 2위(2位)에 이중결합한 구조를 가진다. 카르바페넴계 항생제는 그람양성균에서 그람음성균, 혐기성균까지 폭이 넓은 항균활성을 나타내고, β-락타마아제(β-lactamase)에서도 안정적인 것이 특징이다.In the present invention, the Pseudomonas aeruginosa may be an antibiotic-resistant Pseudomonas aeruginosa, preferably a beta-lactam antibiotic resistant Pseudomonas aeruginosa, and more preferably a carbapenem antibiotic resistant Pseudomonas aeruginosa. Clinically, carbapenem antibiotics are similar to the penicillin skeleton, so there is a β-lactam ring and a 5-membered ring, but the S (sulfur) atom of the 5-membered ring has a C (carbon) (2-position). Carbapenem antibiotics exhibit broad antibacterial activities ranging from Gram-positive bacteria to Gram-negative bacteria and anaerobic bacteria, and are stable in β-lactamase.

본 발명에서, 상기 카르바페넴계 항생제는 이미페넴, 파니페넴(panipenem), 베타니프론(betanipron), 메로페넴(meropenem) 등일 수 있으며, 바람직하게는 이미페넴일 수 있으나, 이에 본 발명이 제한되는 것은 아니다. 본 발명의 박테리오파지 PA4는 최근 문제가 되고 있는 항생제 내성, 특히 카르바페넴 항생제에 대한 내성균에 대한 특이적인 사멸능을 가지므로 상기 균에 의한 감염성 질병의 예방 또는 치료용 약학적 조성물을 제공할 수 있으나, 이에 본 발명이 제한되는 것은 아니다.In the present invention, the carbapenem antibiotic may be imipenem, panipenem, betanipron, meropenem, and the like, preferably imipenem, but the present invention is not limited thereto. Since the bacteriophage PA4 of the present invention has antibiotic resistance, which is a recent problem, specifically a killing effect against resistant bacteria against carbapenem antibiotics, a pharmaceutical composition for preventing or treating infectious diseases caused by the bacteria can be provided , And thus the present invention is not limited thereto.

본 발명에서, 녹농균에 의한 감염성 질병은 패혈증, 전신감염, 기도감염, 낭포성 섬유증, 녹농균 모낭염, 골수염, 괴저성 농창(ecthyma gangraenosum), 방광염, 중이염, 농흉(empyema), 폐렴, 뇌막염, 복막염, 각막염, 내안구염 및 균혈증을 포함하나 이에 본 발명이 제한되는 것은 아니고, 녹농균에 의하여 발생할 수 있는 이차감염을 모두 포함한다.In the present invention, infectious diseases caused by Pseudomonas aeruginosa include septicemia, systemic infections, airway infections, cystic fibrosis, pseudomonas aeruginosa, osteomyelitis, ecthyma gangraenosum, cystitis, otitis media, empyema, pneumonia, meningitis, Keratitis, internal organs, and bacteremia. However, the present invention is not limited thereto, and includes all secondary infections that may be caused by P. aeruginosa.

본 발명의 약학적 조성물은 1×103 내지 1×1010 PFU/mL의 박테리오파지를 포함하며, 바람직하게는 1×106 내지 1×109 PFU/mL의 박테리오파지를 포함한다. 본 발명에 사용된 용어, PFU(plaque forming unit)는 박테리오파지가 플라크를 형성하는 것을 수치화한 단위이다.The pharmaceutical composition of the present invention contains bacteriophage of 1 × 10 3 to 1 × 10 10 PFU / mL, preferably 1 × 10 6 to 1 × 10 9 PFU / mL of bacteriophage. The term " PFU (plaque forming unit) " used in the present invention is a unit in which bacteriophages form a plaque.

본 발명의 용어 예방이란 조성물의 투여로 질병을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다.The term " prophylactic " of the present invention means all actions that inhibit disease or delay the onset of the disease by administration of the composition.

본 발명의 용어 치료란 조성물의 투여로 상기 질병의 증세가 호전되거나 상기 질병의 억제 또는 경감 및 이롭게 변경되는 모든 행위를 의미한다.The term " treatment " of the present invention refers to any action that improves or alleviates or alleviates the symptoms of the disease upon administration of the composition.

본 발명의 약학적 조성물은 약학적으로 허용 가능한 담체를 추가로 포함할 수 있다.The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier.

본 발명에서 용어, 약학적으로 허용 가능한 담체란 생물체를 자극하지 않고 투여 화합물의 생물학적 활성 및 특성을 저해하지 않는 담체 또는 희석제를 의미한다. 액상 용액으로 제제화되는 조성물에 있어서 허용되는 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 덱스트로오스 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.The term pharmaceutically acceptable carrier, as used herein, means a carrier or diluent that does not irritate the organism and does not interfere with the biological activity and properties of the administered compound. Examples of the pharmaceutical carrier which is acceptable for the composition to be formulated into a liquid solution include sterilized and sterile water, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.

본 발명의 약학적 조성물은 질환 부위에의 도포 또는 분무하는 방법으로 이용할 수 있으며, 그 밖에 비강 분무, 경구 투여 또는 비경구 투여를 통해 투여할 수도 있으며, 비경구 투여의 경우 정맥 내 투여, 복강 내 투여, 근육 내 투여, 피하 투여 또는 국부 투여를 이용하여 투여할 수 도 있다.The pharmaceutical composition of the present invention can be used as a method of applying or spraying on a diseased site, or may be administered through nasal spray, oral administration or parenteral administration. In the case of parenteral administration, intravenous administration, intraperitoneal administration Administration, intramuscular administration, subcutaneous administration or local administration.

상기 비강 분무의 경우 일정량의 박테리오파지 PA4를 물에 희석하여 분무기나 분무 시스템을 통해 비강으로 흡수 되도록 할 수 있다. 상기 비강 분무를 위한 비강 분무제 또는 호흡기용 제형으로는 에어로졸제 등을 들 수 있다.In the case of the nasal spray, a certain amount of bacteriophage PA4 can be diluted in water and absorbed into the nasal cavity through a sprayer or spray system. Examples of the nasal spray agent for the nasal spray or the aerosol agent for the respiratory system are mentioned.

상기 비강 분무제 또는 호흡기용 제형은, 수분산된 농축물 또는 습윤 분말을 분산시키기 위한 추진제 및/또는 기타 첨가제를 추가로 포함할 수 있다.The nasal spray or respiratory formulation may further comprise a propellant and / or other additives for dispersing the water-dispersed concentrate or wet powder.

본 발명의 약학적 조성물의 적합한 도포, 분무 및 투여량은 제제화 방법, 투여 방식, 대상이 되는 동물 및 환자의 연령, 체중, 성, 질병 증상의 정도, 음식, 투여시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사나 수의사는 목적하는 치료에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다.The appropriate application, spray and dose of the pharmaceutical composition of the present invention may vary depending on factors such as formulation method, administration method, age, body weight, sex, disease symptom level, food, administration time, administration route, Response sensitivities, and the ordinarily skilled physician or veterinarian can readily determine and prescribe dosages effective for the desired treatment.

본 발명의 약학적 조성물을 유효성분으로 포함하는 경구 투여용 제형으로는, 예를 들어 정제, 트로키제, 로렌지, 수용성 또는 유성현탁액, 조제분말 또는 과립, 에멀젼, 하드 또는 소프트 캡슐, 시럽 또는 엘릭시르제로 제제화할 수 있다. 정제 및 캡슐 등의 제형으로 제제화하기 위해, 락토오스, 사카로오스, 솔비톨, 만니톨, 전분, 아밀로펙틴, 셀룰로오스 또는 젤라틴과 같은 결합제, 디칼슘 포스페이트와 같은 부형제, 옥수수 전분 또는 고구마 전분과 같은 붕괴제, 스테아르산 마그네슘, 스테아르산 칼슘, 스테아릴푸마르산 나트륨 또는 폴리에틸렌글리콜 왁스와 같은 윤활유를 포함할 수 있으며, 캡슐 제형의 경우 상기 언급한 물질 외에도 지방유와 같은 액체 담체를 더 함유할 수 있다.Examples of formulations for oral administration comprising the pharmaceutical composition of the present invention as an active ingredient include tablets, troches, lozenges, aqueous or oily suspensions, prepared powders or granules, emulsions, hard or soft capsules, syrups or elixirs It can be formulated into a zero. A binder such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose or gelatin, an excipient such as dicalcium phosphate, a disintegrating agent such as corn starch or sweet potato starch, a disintegrant such as magnesium stearate , Calcium stearate, sodium stearyl fumarate or polyethylene glycol wax. In the case of a capsule formulation, in addition to the above-mentioned materials, a liquid carrier such as a fatty oil may be further contained.

본 발명의 약학적 조성물을 유효성분으로 포함하는 비경구 투여용 제형으로는, 피하주사, 정맥주사 또는 근육 내 주사 등의 주사용 형태, 좌제 주입방식 또는 호흡기를 통하여 흡입이 가능하도록 하는 에어로졸제 등 스프레이용으로 제제화할 수 있다. 주사용 제형으로 제제화하기 위해서는 본 발명의 조성물을 안정제 또는 완충제와 함께 물에서 혼합하여 용액 또는 현탁액으로 제조하고, 이를 앰플 또는 바이알의 단위 투여용으로 제제화할 수 있다. 에어로졸제 등의 스프레이용으로 제형화하는 경우, 수분산된 농축물 또는 습윤 분말이 분산되도록 추진제 등이 첨가제와 함께 배합될 수 있다.Examples of the formulations for parenteral administration containing the pharmaceutical composition of the present invention as an active ingredient include injection forms such as subcutaneous injection, intravenous injection or intramuscular injection, aerosol formulations such as a suppository injection method or a respiratory apparatus It can be formulated for spraying. For formulation into injectable formulations, the compositions of the present invention may be formulated as solutions or suspensions in water with stabilizers or buffers in water, and formulated for unitary administration of ampoules or vials. When formulated for spraying, such as an aerosol formulation, a propellant or the like may be formulated with the additive such that the water-dispersed concentrate or wet powder is dispersed.

또한, 본 발명은 상기 박테리오파지 PA4를 포함하는, 항생용 조성물을 제공한다. In addition, the present invention provides an antibiotic composition comprising the bacteriophage PA4.

본 발명에서, 용어 항생용 조성물은 약제 형태로 동물에게 제공되어 균을 사멸시킬 수 있는 제제를 의미하며, 방부제, 살균제, 항생제 및 항균제를 총칭하는 것이다. In the present invention, the term antibiotic composition refers to a preparation which can be provided to an animal in the form of a drug to kill bacteria, and is collectively referred to as an antiseptic, a bactericide, an antibiotic and an antibacterial agent.

본 발명의 박테리오파지 PA4는 기존 항생제에 비하여 녹농균에 대한 특이성이 매우 높고, 동시에 카르바페넴 항생제 저항성 균에서도 작용하며, 유익균은 죽이지 않으면서 특정 병원균만 사멸시킬 수 있다. 아울러, 약물 내성 내지 저항성을 유도하지 않아, 기존의 항생물질에 비하여 제품수명(life cycling)이 긴 신규 항생제로서 이용될 수 있다는 이점이 있다.The bacteriophage PA4 of the present invention has a higher specificity to P. aeruginosa than that of conventional antibiotics and also acts on carbapenem antibiotic resistant bacteria and can kill only specific pathogens without killing useful bacteria. In addition, it has an advantage that it can be used as a new antibiotic with a longer life cycle than conventional antibiotics because it does not induce drug resistance or resistance.

또한, 본 발명은 상기 박테리오파지 PA4를 포함하는, 사료 첨가용 조성물을 제공한다.The present invention also provides a composition for feed addition comprising the bacteriophage PA4.

축산, 수산업에서 사용되는 사료 첨가용 항생제는 질병의 예방 목적으로 사용되고 있는데, 예방 목적의 항생제 투여는 내성균 발생 가능성을 높이고 가축에 잔류하는 항생제가 사람에게 전달될 수 있어서 문제이다. 항생제가 육류를 통해 인체에 흡수되면 항생제 내성을 유발해 질병의 확산을 부를 수도 있다. 또한, 사료에 섞어 먹이는 항생제의 종류가 많고 이는 다제 내성균 발생 확률이 높아지는 문제점이 있기 때문에 좀 더 자연 친화적이면서도 기존의 항생제의 사용에서 발생한 문제를 해결할 새로운 사료 첨가용 항생물질로서 본 발명의 상기 박테리오파지 PA4를 이용할 수 있다.Antibiotics for feed additive used in animal husbandry and fisheries are used for the prevention of diseases. The administration of antibiotics for prevention is problematic because it increases the possibility of producing resistant bacteria and antibiotics remaining in the livestock can be delivered to humans. If antibiotics are absorbed into the body through meat, they may cause antibiotic resistance and spread the disease. In addition, since there are many types of antibiotics to be mixed with feed, there is a problem that the probability of occurrence of multidrug-resistant bacteria is increased. Therefore, as a new food additive antibiotic substance which is more environmentally friendly and solves the problems caused by the use of existing antibiotics, Can be used.

또한, 본 발명은 상기 사료 첨가용 조성물을 포함하는 사료를 제공할 수 있으며, 본 발명의 사료는 박테리오파지를 사료 첨가제 형태로 따로 제조하여 사료에 혼합시키거나, 사료 제조 시 직접 첨가시켜 제조할 수 있다. 본 발명의 사료 내 박테리오파지는 액상 또는 건조 상태일 수 있으며, 바람직하게는 건조된 분말형태이다. 건조방법은 통풍건조, 자연건조, 분무건조 및 동결건조가 가능하지만, 이에 제한되는 것은 아니다. 본 발명의 박테리오파지는 분말형태로 사료 중량의 0.05 내지 10 중량%, 바람직하게는 0.1 내지 2 중량%의 성분비로 혼합될 수 있다. 또한, 상기 사료는 본 발명의 박테리오파지 외에 사료의 보존성을 높일 수 있는 통상의 첨가제들을 추가로 포함할 수 있다.In addition, the present invention can provide a feed comprising the feed composition, and the feed of the present invention can be prepared by separately preparing bacteriophage as a feed additive and mixing the feed into the feed, . The bacteriophage in the feed of the present invention may be in a liquid or dry state, preferably in the form of a dried powder. Drying methods include, but are not limited to, air drying, natural drying, spray drying and freeze drying. The bacteriophage of the present invention may be mixed in powder form in a composition ratio of 0.05 to 10% by weight, preferably 0.1 to 2% by weight of the feed weight. In addition to the bacteriophages of the present invention, the feed may further include conventional additives that can enhance the preservability of the feed.

본 발명의 사료 첨가용 조성물에는 비병원성의 다른 미생물이 추가로 첨가될 수 있다. 첨가될 수 있는 미생물로는 단백질 분해 효소, 지질 분해효소 및 당 전환 효소를 생산할 수 있는 바실러스 서브틸리스(Bacillus subtilis)와 같은 고초균, 소의 위와 같은 혐기적 조건에서 생리적 활성 및 유기물 분해능이 있는 락토바실러스 균주(Lactobacillus sp.), 가축의 체중을 증가시키며 우유의 산유량을 늘리고 사료의 소화 흡수율을 높이는 효과를 보여주는 아스퍼질러스 오리자에(Aspergillus oryzae)와 같은 사상균 및 사카로미세스 세레비지에(Saccharomyces cerevisiae)와 같은 효모로 구성된 군으로부터 선택될 수 있다.In the composition for feed addition of the present invention, microorganisms other than non-pathogenic microorganisms may be further added. Examples of microorganisms that can be added include lactobacilli such as Bacillus subtilis capable of producing proteolytic enzymes, lipolytic enzymes and glycosyltransferases, lactobacilli having physiological activity and organic resolution at anaerobic conditions such as bovine, ( Lactobacillus sp.), Filamentous fungi such as Aspergillus oryzae , which increase the body weight of livestock and increase the milk yield of milk and increase digestion rate of feed, and Saccharomyces cerevisiae ). ≪ / RTI >

본 발명의 박테리오파지 PA4를 포함하는 사료에는 식물성으로는 곡물류, 근과류, 식품가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류, 곡물부산물류 등이 있으며, 동물성으로는 단백질류, 무기물류, 유지류, 광물성류, 단세포 단백질, 동물성 플랑크톤류, 남은 음식물 등이 있으며 이에 제한되는 것은 아니다.Examples of the feedstuffs containing bacteriophage PA4 of the present invention include cereals, muscle roots, food processing, logistics, algae, fibers, pharmaceuticals, and fats, oils, pastes, But are not limited to, proteins, mineralogy, oils, mineralogy, unicellular proteins, zooplankton, and remnants.

본 발명의 사료 첨가용 조성물에는 품질 저하를 방지하기 위하여 첨가하는 결착제, 유화제, 보존제 등이 포함될 수 있고, 효용 증대를 위하여 사료에 첨가하는 아미노산제, 비타민제, 효소제, 생균제, 향미제, 비단백태질소화합물, 규산염제, 완충제, 착색제, 추출제, 올리고당 등이 있으며, 그 외에도 사료 혼합제 등을 추가로 포함할 수 있다.The composition for feed addition of the present invention may contain a binder, an emulsifying agent, a preservative, etc. added to prevent deterioration of quality. An amino acid, a vitamin, an enzyme, a probiotic, a flavoring agent, A nitrogen compound, a silicate, a buffer, a coloring agent, an extracting agent, and an oligosaccharide. In addition, a feed mixture may be further included.

또한, 본 발명은 박테리오파지 PA4를 포함하는, 음용수 첨가제를 제공한다.The present invention also provides a drinking water additive comprising bacteriophage PA4.

본 발명의 음용수 첨가제는 상기 박테리오파지 PA4 또는 이를 포함하는 조성물을 음용수 첨가제 형태로 따로 제조하여 사료 또는 음용수에 혼합하는 방식으로 사용되거나, 음용수 제조 시 직접 첨가하는 방식으로 사용할 수 있다. 상기와 같이 음용수에 혼합하여 공급함으로써 지속적으로 녹농균, 특히 카르바페넴 내성 녹농균의 숫자를 감소시킬 수 있는 효과가 있다.The additive for drinking water of the present invention can be used either by preparing the bacteriophage PA4 or a composition containing the bacteriophage PA4 separately in the form of a drinkable water additive, mixing the mixture with feed or drinking water, or adding the bacteriophage PA4 directly in the production of drinking water. By mixing and supplying the drinking water as described above, there is an effect that the number of P. aeruginosa, especially carbapenem resistant P. aeruginosa can be reduced.

본 발명에서 음용수는 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용되는 음용수를 사용할 수 있다.In the present invention, the drinking water is not particularly limited, and drinking water commonly used in the art can be used.

또한, 본 발명은 상기 박테리오파지 PA4를 포함하는, 소독제를 제공한다.The present invention also provides a disinfecting agent comprising the bacteriophage PA4.

녹농균, 특히 카르바페넴 내성 녹농균에 특이적 사멸능을 갖는 본 발명의 박테리오파지 PA4를 포함하는 소독제는 병원감염을 막기 위한 병원 및 보건용의 소독제로 유용하게 사용될 수 있고 일반 생활 소독제, 식품 및 조리 장소 및 설비의 소독제, 양계장, 축사 등의 건물, 축체, 음수, 깔짚, 난좌, 운반차량, 식기 등의 각종 생육 용품의 소독 등에 사용될 수 있다.The disinfectant containing the bacteriophage PA4 of the present invention, which has a specific killing ability against Pseudomonas aeruginosa, especially carbapenem-resistant Pseudomonas aeruginosa, can be effectively used as a disinfectant for hospital and public health to prevent hospital infection, And disinfection of various kinds of growth articles such as disinfectants, poultry houses, barns, etc., buildings, shaft bodies, negative water, litter, stairs, transportation vehicles, tableware and the like.

또한, 본 발명은 상기 박테리오파지 PA4를 포함하는, 세척제를 제공한다.The present invention also provides a detergent comprising the bacteriophage PA4.

본 발명의 박테리오파지 PA4는 녹농균에 특이적 사멸능을 가지므로, 녹농균에 노출되었거나 노출될 가능성이 있는 조류의 피부 표면 또는 신체 각 부위 등을 세척하는 용도로도 사용될 수 있다.Since the bacteriophage PA4 of the present invention has a specific killing ability against P. aeruginosa, it can also be used for washing the skin surface or body parts of birds which are exposed or exposed to P. aeruginosa.

또한, 본 발명은 상기 박테리오파지 PA4를 개체에 투여하는 단계를 포함하는, 녹농균에 의한 감염성 질병의 예방 또는 치료 방법을 제공한다.The present invention also provides a method for preventing or treating an infectious disease caused by P. aeruginosa, comprising the step of administering the bacteriophage PA4 to an individual.

본 발명에서, 용어 "개체"는 녹농균에 의한 감염성 질병이 발병될 수 있는 모든 개체를 의미하는 것으로 인간을 포함한 포유동물, 가축류 또는 가금류를 포함하나, 이에 제한되는 것은 아니다. In the present invention, the term "individual" means any individual to which an infectious disease caused by P. aeruginosa can be developed, including, but not limited to, mammals including humans, livestock or poultry.

상기 용어 "가축류"는 인간에 의하여 순화, 개량되어 사람과 함께 공동생활을 하는 유용한 동물을 지칭하는 개념으로, 예를 들어, 돼지, 소, 닭, 말, 오리 또는 개 등을 포함하나, 이에 제한되는 것은 아니다.The term " livestock animal "is intended to refer to useful animals that are refined and improved by humans to co-live with humans, including, for example, pigs, cows, chickens, horses, ducks or dogs, It is not.

상기 용어 "가금류"는, 가축 중 조류에 속하는 동물을 총칭하여 이르는 개념으로, 예를 들어, 닭, 오리, 꿩, 메추리, 타조, 거위 또는 칠면조 등을 포함하나, 이에 제한되는 것은 아니다.The term "poultry" includes, but is not limited to, chicken, duck, pheasant, queen, ostrich, goose or turkey.

본 발명의 방법에서 상기 박테리오파지 PA4 또는 조성물은 약학적 제제의 형태로 동물에게 투여되거나, 가축의 사료 또는 음용수에 혼합하여 이를 섭식시키는 방법을 통해 투여될 수 있다.In the method of the present invention, the bacteriophage PA4 or the composition may be administered to an animal in the form of a pharmaceutical preparation, or mixed with feed or drinking water of a livestock and fed.

본 발명의 방법에서 상기 박테리오파지 PA4 또는 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 경구 또는 비경구의 다양한 경로를 통하여 투여될 수 있으며, 구체적으로, 구강, 직장, 국소, 정맥 내, 복강 내, 근육 내, 동맥 내, 경피, 비측 내, 흡입 등을 통해 통상적인 방식으로 투여될 수 있다.In the method of the present invention, the administration route of the bacteriophage PA4 or composition can be administered through various routes of oral or parenteral administration as long as it can reach the target tissues. Specifically, oral administration, rectal administration, topical administration, intravenous, Intravenous, intramuscular, intraarterial, transdermal, intranasal, inhalation, and the like.

본 발명의 방법에 투여되는 상기 박테리오파지 PA4의 적합한 총 1일 사용량은 올바른 의학적 판단범위 내에서 처치의에 의해 결정될 수 있다는 것은 당업자에게 자명한 일이다. 특정 개체에 대한 구체적인 치료적 유효량은 달성하고자 하는 반응의 종류와 정도, 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여시간, 투여 경로 및 조성물의 분비율, 치료기간, 구체적 조성물과 함께 사용되거나 동시 사용되는 약물을 비롯한 다양한 인자와 의약 분야에 잘 알려진 유사 인자에 따라 다르게 적용하는 것이 바람직하다.It will be apparent to those skilled in the art that the appropriate total daily dose of the bacteriophage PA4 administered in the methods of the present invention can be determined by treatment within the scope of sound medical judgment. The specific therapeutically effective amount for a particular individual will depend upon the type and extent of the response to be achieved, the age, weight, general health, sex and diet of the patient, the time of administration, the route of administration and the fraction of the route of administration, It is preferable to apply differently depending on various factors including drugs used or co-used and similar factors well known in the medical field.

중복되는 내용은 본 명세서의 복잡성을 고려하여 생락하며, 본 명세서에서 달리 정의되지 않은 용어들은 본 발명이 속하는 기술 분야에서 통상적으로 사용되는 의미를 갖는 것이다.The redundant contents are taken into consideration in the complexity of the present specification, and terms not otherwise defined herein have the meanings commonly used in the art to which the present invention belongs.

이하, 본 발명을 실시예, 제제예에 의해 상세히 설명한다. 단, 하기 실시예, 제제예는 본 발명을 예시하는 것일 뿐 본 발명의 내용이 하기 실시예, 제제예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail with reference to Examples and Preparation Examples. However, the following examples and preparative examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following examples and preparative examples.

실시예 1: 신규한 박테리오파지의 분리 및 배양Example 1: Isolation and culture of novel bacteriophages

1.1 박테리오파지의 스크리닝 및 분리1.1 Screening and separation of bacteriophages

카르바페넴(carbapenem)계 항생제인 이미페넴(imipenem) 내성 녹농균(슈도모나스 에루지노사(Pseudomonas aeruginosa))에 특이적인 박테리오파지를 스크리닝 및 분리하기 위해서 용균반 분석을 수행하였다. 시료는 박테리오파지가 존재할 것으로 예상되는 하수처리장, 도계장 및 양계농장 부근의 하수로부터 채취하였으며, 박테리오파지 분리에 사용된 이미페넴 내성 녹농균은 아시아태평양 감염재단에서 분양받은 것을 사용하였다.Sputum analysis was performed to screen and isolate bacteriophages specific to the carbapenem antibiotic imipenem-resistant P. aeruginosa ( Pseudomonas aeruginosa ). Samples were collected from sewage treatment plants, slaughterhouses and poultry farms where bacteriophages are expected to be present. Imipenem resistant P. aeruginosa used for bacteriophage isolation was purchased from the Asia Pacific Infection Foundation.

구체적으로, 채취한 시료를 균질화 한 후 상기 녹농균과 함께 35℃에서 하룻밤 동안 진탕배양 하였다. 상기 배양액을 4,000 rpm으로 20분간 원심분리한 후, 상등액을 공극(pore) 크기가 0.45 μm인 필터를 이용하여 여과하여 시료 여과액을 얻었다.Specifically, the collected samples were homogenized and incubated with the P. aeruginosa at 35 DEG C for one night with shaking. The culture solution was centrifuged at 4,000 rpm for 20 minutes, and the supernatant was filtered using a filter having a pore size of 0.45 μm to obtain a sample filtrate.

전배양된 이미페넴 내성 녹농균 150 μL를 취해서 멸균된 튜브에 넣고 3 mL의 BHI 탑 아가(top agar) (뇌 심장 침출액(brain heart infusion) (뇌 침출 고체 12.5 g, 소 심장 침출액 고체 5.0 g, 프로테오스 펩톤 10.0 g, 글루코스 2.0 g, 염화나트륨 5.0 g, 인산나트륨 2.5 g/L) + 0.6% 아가)를 첨가하여 잘 혼합한 후 미리 만들어 둔 2% BHI 아가 플레이트에 중층하였다. 실온에서 30분간 방치한 후 상기 시료 여과액을 각각 10 μL씩 점적하고, 다시 실온에서 30분간 방치한 후 35℃에서 24시간 동안 배양하여 박테리오파지의 유무를 확인하였다. 그 결과는 도 1에 나타내었다.150 μL of pre-cultured imipenem-resistant Pseudomonas aeruginosa was placed in a sterile tube and placed in a sterile tube, and 3 mL of BHI top agar (brain heart infusion: 12.5 g of brain leaching solids, 5.0 g of bovine leachate solids, 10.0 g of streptone, 2.0 g of glucose, 5.0 g of sodium chloride, and 2.5 g / L of sodium phosphate) + 0.6% agar) was added thereto and the mixture was layered on 2% BHI agar plates previously prepared. After allowing to stand at room temperature for 30 minutes, the sample filtrate was dropped by 10 μL each. Each sample was left at room temperature for 30 minutes and then cultured at 35 ° C. for 24 hours to confirm presence or absence of bacteriophages. The results are shown in Fig.

한편, 박테리오파지의 존재를 확인한 시료로부터 박테리오파지를 순수 분리하기 위해서 소프트 아가 오버레이(soft agar overlay)법을 이용하였다. 박테리오파지가 존재하는 것으로 확인된 시료를 식염수로 적절히 희석하여 각 희석단의 시료 희석액 100 μL를 취하고, 대상 세균(이미페넴 내성 녹농균) 배양액 150 μL에 혼합한 후 0.6% BHI 탑 아가 3 mL을 첨가하여 잘 혼합한 뒤, 미리 만들어 둔 2% BHI 아가 플레이트에 중층하여 방치한 후 35℃에서 24시간 배양하였다. 배양한 각 플레이트에서 형성된 용균반을 확인한 후, 이를 선택하여 400 μL의 SM 완충액 (NaCl 5.8 g/L; MgSO47H2O 2 g/L; 1M Tris-HCl (pH 7.5) 50 mL)에 현탁하고, 실온에서 4시간 동안 천천히 교반하면서 박테리오파지 용액을 회수한 후 4,000 rpm으로 20분간 원심분리하여 상등액만 취하고 이를 0.2 μm 필터로 여과하여 최종 박테리오파지 용액을 회수하였다. 이렇게 얻어진 최종 박테리오파지의 용균반을 확인한 결과를 도 2에 나타내었다.On the other hand, a soft agar overlay method was used to purify the bacteriophage from the sample which confirmed the existence of the bacteriophage. A sample of which the bacteriophage was confirmed to be present was diluted appropriately with saline, 100 μL of sample dilution at each dilution stage was taken, mixed with 150 μL of the bacterial (imipenem resistant P. aeruginosa) culture, and 3 mL of 0.6% BHI topa After mixing, the mixture was allowed to stand in a 2% BHI agar plate that had been previously prepared, followed by incubation at 35 ° C for 24 hours. After incubation, the supernatant was added to 400 μL of SM buffer (NaCl 5.8 g / L; MgSO 4 7H 2 O 2 g / L; 1M Tris-HCl (pH 7.5) , And the bacteriophage solution was recovered by slowly stirring at room temperature for 4 hours. The bacteriophage solution was centrifuged at 4,000 rpm for 20 minutes to collect only the supernatant, which was then filtered with a 0.2 μm filter to recover the final bacteriophage solution. FIG. 2 shows the result of checking the thus obtained final bacteria bacteriophage.

도 1 및 2에 나타낸 바와 같이, 2-4 mm의 크기를 가지는 용균반을 형성하는 박테리오파지를 확인하였고, 상기 박테리오파지는 카르바페넴계 항생제인 이미페넴 내성 녹농균에 특이적인 용균능을 갖는 박테리오파지임을 확인하였다.As shown in FIG. 1 and FIG. 2, bacteriophages forming a fungus having a size of 2-4 mm were identified, and it was confirmed that the bacteriophage was a bacteriophage having a specific capacity for imipenem-resistant P. aeruginosa, which is a carbapenem antibiotic.

1.2 박테리오파지의 대량 배양 및 정제1.2 Bulk culture and purification of bacteriophages

상기 실시예　1.1에서 확인한 카르바페넴계 항생제인 이미페넴 내성 녹농균 특이적 박테리오파지를 대량 배양하기 위하여, 1.1에서 회수한 최종 박테리오파지 배양액을 1.0x107 PFU/mL로 희석한 후 전배양된 이미페넴 내성 녹농균 1.0x109 CFU/mL과 혼합하여 MOI(Multiplicity of infection)가 0.01이 되도록 하여 35℃에서 120 rpm으로 9시간 동안 배양하였다. 배양이 종료된 후 배양액 전량을 6,000 rpm으로 30분간 원심분리하여 상등액을 수득하였고, 이를 0.2 μm 필터로 여과하여 최종 박테리오파지 배양액을 회수하였다. 분리된 박테리오파지를 박테리오파지 PA4(Bacteriophage PA4)로 명명하고, 2016년 10월 21일 한국미생물보존센터 (Korean Culture Center of Microorganisms, 서울, 한국)에 기탁하고 수탁번호 KFCC11697P를 부여받았다.In order to mass-culture the imipenem-resistant P. aeruginosa-specific bacteriophage, which is the carbapenem antibiotic identified in Example 1.1 above, the final bacteriophage culture recovered at 1.1 was diluted to 1.0 x 10 < 7 > After dilution with PFU / mL, the cells were mixed with 1.0 × 10 9 CFU / mL of pre-cultured imipenem-resistant P. aeruginosa and cultured at 35 ° C. and 120 rpm for 9 hours with MOI (multiplicity of infection) of 0.01. After the culture was completed, the whole culture was centrifuged at 6,000 rpm for 30 minutes to obtain a supernatant, which was then filtered with a 0.2 μm filter to recover the final bacteriophage culture. The isolated bacteriophage was named bacteriophage PA4 (Bacteriophage PA4) and deposited with the Korean Culture Center of Microorganisms (Seoul, Korea) on Oct. 21, 2016, and received the accession number KFCC11697P.

실시예 2: 박테리오파지 PA4의 전체 유전자 분석Example 2: Whole gene analysis of bacteriophage PA4

박테리오파지 PA4의 전체 유전자를 분석하기 위해, 박테리오파지 PA4 배양액에 20 mM EDTA, 50 μg/mL의 프로테나아제 K, 0.5%(w/v) SDS를 가한 후, 50℃에서 1시간 동안 정치하였다. 동량의 페놀-클로로포름-이소프로필 알코올 (25:24:1)과 혼합한 후 실온에서 12,000 rpm으로 10분간 원심분리하여 상등액을 회수하였다. 회수된 상등액을 동일 부피의 페놀-클로로포름-이소프로필 알코올 (25:24:1)과 혼합하여 실온에서 12,000 rpm으로 10분간 원심분리한 후 상등액을 회수하고, 상기 상등액에 3M 소듐 아세테이트를 전체 부피의 10%(v/v)가 되도록 가한 후 혼합하였다. 여기에 2배 부피의 차가운 95% 에탄올을 가하여 혼합한 뒤 -20℃에서 1시간 동안 정치하였다. 반응이 끝난 후 0℃에서 10분간 12,000 rpm으로 원심분리하여 침전물을 획득하였고, 차가운 70% 에탄올로 2회 세척한 뒤 에탄올을 완전히 제거하여 DNA 펠렛을 회수하였다. 회수한 펠렛을 최종 부피가 50 μL가 되도록 TE 완충액 (Tris-EDTA, pH 8.0)에 용해시킨 후 DNA 농도를 측정하였다. 전체 유전자 분석을 위해 PacBioRSII 를 이용하여 유전자 시퀀싱을 시행하였다(마크로젠, 한국). 시퀀싱 결과로 얻은 박테리오파지 PA4의 유전자 맵을 도 3에 나타내었다.In order to analyze the entire gene of bacteriophage PA4, 20 mM EDTA, 50 μg / mL proteinase K and 0.5% (w / v) SDS were added to the bacteriophage PA4 culture and left at 50 ° C. for 1 hour. The mixture was mixed with an equal amount of phenol-chloroform-isopropyl alcohol (25: 24: 1) and centrifuged at 12,000 rpm for 10 minutes at room temperature to recover the supernatant. The recovered supernatant was mixed with an equal volume of phenol-chloroform-isopropyl alcohol (25: 24: 1) and centrifuged at 12,000 rpm for 10 minutes at room temperature. The supernatant was recovered and 3M sodium acetate was added to the supernatant in a total volume 10% (v / v). The mixture was mixed with 2 volumes of cold 95% ethanol, and the mixture was allowed to stand at -20 DEG C for 1 hour. After the reaction was completed, the precipitate was collected by centrifugation at 12,000 rpm for 10 minutes at 0 ° C., washed twice with cold 70% ethanol, and then the ethanol was completely removed to recover the DNA pellet. The recovered pellet was dissolved in TE buffer (Tris-EDTA, pH 8.0) to a final volume of 50 μL, and the DNA concentration was measured. Gene sequencing was performed using PacBioRSII for whole gene analysis (Macrogen, Korea). The gene map of bacteriophage PA4 obtained as a result of sequencing is shown in Fig.

도 3에 나타낸 바와 같이, 박테리오파지 PA4의 전체 유전자의 크기는 66,485 bp 이며, GC함량이 56%, 전체 ORFs의 수는 95개임을 확인하였다. 분석한 박테리오파지 PA4의 전체 유전자 서열을 서열번호 1로 나타내었다.As shown in FIG. 3, it was confirmed that the size of the entire gene of bacteriophage PA4 was 66,485 bp, the GC content was 56%, and the total ORFs were 95. The entire gene sequence of the analyzed bacteriophage PA4 is shown in SEQ ID NO: 1.

실시예 3: 박테리오파지 PA4의 형태학적 특성Example 3: Morphological characteristics of bacteriophage PA4

박테리오파지 PA4의 형태학적 특성을 알아보기 위해, 상기 실시예 1-2에서 얻은 배양액을 2.5% 파라포름알데하이드-글루타알데하이드(glutaraldehyde) (4℃, 인산 버퍼, pH7.2) 용액으로 2시간 동안 고정하였고, 그 후 완충액(0.1 M 인산 버퍼, pH7.2)에서 10분씩 3회 세척한 후 1% OsO4(25℃, 0.1M 인산 버퍼, pH7.2) 용액으로 2시간 동안 추가적으로 고정하였다. 이를 상기 완충액과 동일한 완충액으로 수회 세척한 후에 에탄올로 탈수하였으며, 프로필렌 옥사이드로 치환하여 Epon-812로 포매(ebedding)한 후 60℃ 오븐에서 36시간 동안 중합 반응을 수행하였다. 초마이크로톰(ultramicrotome; ULTRACUT E, Leica)을 이용하여 상기 포매된 조직을 초박편 형태로 제작하였으며, 이를 우라닐 아세테이트(Uranyl acetate) 및 시트르산납(lead citrate)에서 염색하고 건조시킨 후, 투과전자현미경(CM 20, Philips, Bio-Transmission electron microscope, 100 kV, 120,000~250,000)으로 관찰하였다. 그 결과를 도 4에 나타내었다.In order to examine the morphological characteristics of bacteriophage PA4, the culture obtained in Example 1-2 was fixed with a solution of 2.5% paraformaldehyde-glutaraldehyde (4 ° C, phosphate buffer, pH 7.2) for 2 hours , And then washed three times for 10 minutes in buffer (0.1 M phosphate buffer, pH 7.2), and further fixed with 1% OsO 4 (25 ° C, 0.1 M phosphate buffer, pH 7.2) solution for 2 hours. This was washed several times with the same buffer as the above buffer, dehydrated with ethanol, substituted with propylene oxide, embedded in Epon-812, and polymerized in an oven at 60 ° C for 36 hours. The embedded tissues were prepared in the form of supramolecular fragments using ultramicrotome (ULTRACUT E, Leica), stained with Uranyl acetate and lead citrate, dried, and examined by transmission electron microscope (CM 20, Philips, Bio-Transmission electron microscope, 100 kV, 120,000 ~ 250,000). The results are shown in Fig.

도 4에 나타낸 바와 같이, 박테리오파지 PA4는 130-150 nm의 크기로, 정이십면체의 머리를 가지며 수축성의 꼬리를 가지는 형태인 마이오비리대(Myoviridae)에 속함을 확인하였다.As shown in FIG. 4, bacteriophage PA4 was found to belong to Myoviridae, which is 130-150 nm in size and has a truncated icosahedral head and a contractile tail.

실시예 4: 박테리오파지 PA4의 단백질 패턴 분석Example 4: Protein pattern analysis of bacteriophage PA4

박테리오파지 PA4의 단백질 패턴을 분석하기 위해, 1.0x1010 PFU/mL로 준비된 박테리오파지 PA4 40 μL를 10 μL의 5X 로딩 완충액과 혼합하고, 10분간 끓인 다음 12.5% SDS-PAGE를 수행하였다. SDS-PAGE 수행 후 단백질 전기영동 결과를 도 5에 나타내었다.To analyze the protein pattern of bacteriophage PA4, 40 μL of bacteriophage PA4 prepared to 1.0 × 10 10 PFU / mL was mixed with 10 μL of 5X loading buffer, boiled for 10 minutes, and then subjected to 12.5% SDS-PAGE. The results of SDS-PAGE and protein electrophoresis are shown in FIG.

도 5에 나타낸 바와 같이, 박테리오파지 PA4는 90 kDa, 60 kDa, 43 kDa, 23 kDa 그리고 16 kDa 크기의 주요 단백질을 가지는 것을 확인하였다.As shown in FIG. 5, bacteriophage PA4 has major proteins of 90 kDa, 60 kDa, 43 kDa, 23 kDa and 16 kDa in size.

실시예 5: 박테리오파지 PA4의 다양한 세균에 대한 감염성 조사Example 5: Investigation of infectivity of various bacterium of bacteriophage PA4

박테리오파지 PA4의 다양한 세균에 대한 감염성을 조사하였다.Infection of bacteriophage PA4 against various bacteria was investigated.

우선, 박테리오파지 PA4의 카르바페넴계 항생제 내성 녹농균에 대한 용균 활성을 확인하기 위하여, 소프트 아가 오버레이법을 이용하여 아시아태평양 감염연구소에서 분양받은 이미페넴 내성 녹농균을 대상으로 용균 활성을 확인하였다. 그 결과를 표 1에 나타내었다.First, to confirm the lytic activity of bacteriophage PA4 against carbapenem antibiotic resistant Pseudomonas aeruginosa, we investigated the lytic activity of imipenem resistant P. aeruginosa cultured in Asia Pacific Infection Research Institute using soft agar overlay method. The results are shown in Table 1.

Figure pat00001
Figure pat00001

(+: 용균활성 있음)(+: Lytic activity)

상기 표 1에 나타낸 바와 같이, 본 발명의 박테리오파지 PA4가 이미페넴 내성 녹농균 8개 균주 중 모든 균주에 대해서 용균활성을 나타냄을 통해 본 발명의 박테리오파지 PA4가 이미페넴 내성, 즉 카르바페넴 내성 녹농균에 대하여 탁월한 용균활성을 가짐을 확인하였다.As shown in Table 1, the bacteriophage PA4 of the present invention exhibited a lytic activity against all of the strains of the eight imipenem-resistant P. aeruginosa strains, indicating that the bacteriophage PA4 of the present invention exhibited excellent immunophenemia resistance against carbapenem resistant P. aeruginosa Lt; / RTI > activity.

또한, 박테리오파지 PA4가 다른 속 세균에 대해서도 용균활성을 나타내는지 확인하기 위하여 ㈜옵티팜에서 분리하여 보유하고 있는 균주와 미생물 자원센터 등에서 분양받은 균주를 대상으로 소프트 아가 오버레이법을 통해서 감염성을 확인하였다. 그 결과를 표 2에 나타내었다.In order to confirm whether bacteriophage PA4 exhibits lytic activity against other genus bacterium, the strains isolated from OptiParm Co., Ltd. and purchased from the microorganism resource center were infected with the virus through the soft agar overlay method. The results are shown in Table 2.

Figure pat00002
Figure pat00002

(+: 용균활성 있음, -; 용균활성 없음)(+: Lytic activity, -; lytic activity)

표 2에 나타낸 바와 같이, 본 발명의 박테리오파지 PA4는 카르바페넴계 항생제 내성 녹농균 외에 내성을 갖지 않는 녹농균에 대해서도 용균성을 가지는 것을 확인하였다. 그러나 박테리오파지 PA4는 녹농균 외에 다른 속인 Bacillus cereus, Escherichia coli 및 Lactobacillus plantarum 등의 균주에 대해서는 용균활성이 없는 것을 확인하였다.As shown in Table 2, it was confirmed that the bacteriophage PA4 of the present invention has a fungicidal activity against P. aeruginosa resistant to carbapenem antibiotic-resistant bacteria. However bacteriophage PA4 was confirmed that in addition to the other lay Pseudomonas aeruginosa no lytic activity for the strain, such as Bacillus cereus, Escherichia coli and Lactobacillus plantarum.

따라서, 본 발명의 박테리오파지 PA4는 녹농균에 특이적으로 용균활성을 나타내는 박테리오파지임을 확인하였다.Therefore, it was confirmed that the bacteriophage PA4 of the present invention is a bacteriophage exhibiting a lytic activity specifically against P. aeruginosa.

실시예 6: 박테리오파지 PA4의 pH 안정성 조사Example 6: Investigation of pH stability of bacteriophage PA4

박테리오파지 PA4의 pH 안정성을 확인하기 위하여, 다양한 pH 범위 (pH3, 4, 5, 6, 7, 8, 9)에서 박테리오파지의 수를 측정하였다. 소듐 아세테이트 완충액 및 소듐 포스페이트 완충액을 이용하여 각각의 pH에 맞게 조제한 후 박테리오파지 PA4 배양액을 4.0x109 PFU/mL으로 준비한 다음, 2시간 동안 상온에서 방치하였다. 방치 후 각 반응액을 단계 희석하여 소프트 아가 오버레이법에 의해 타이터(titer) 측정을 수행한 결과를 도 6에 나타내었다.In order to confirm the pH stability of bacteriophage PA4, the number of bacteriophages was measured in various pH ranges (pH 3, 4, 5, 6, 7, 8, 9). Sodium acetate buffer and sodium phosphate buffer, and then the bacteriophage PA4 culture solution was prepared at 4.0 × 10 9 PFU / mL, and then left at room temperature for 2 hours. After allowing to stand, each reaction solution was diluted stepwise, and a titer measurement was performed by soft agar overlay method. The result is shown in Fig.

도 6에 나타낸 바와 같이, 본 발명의 박테리오파지 PA4는 pH3-9의 범위에서 안정한 것을 확인하였다. 이를 통해 박테리오파지 PA4는 pH 안정성이 우수한 박테리오파지임을 알 수 있다.As shown in Fig. 6, it was confirmed that the bacteriophage PA4 of the present invention was stable in the pH range of 3-9. This indicates that bacteriophage PA4 is a bacteriophage having excellent pH stability.

실시예 7: 박테리오파지 PA4의 열 안정성 조사Example 7: Investigation of thermal stability of bacteriophage PA4

박테리오파지 PA4의 열 안정성을 확인하기 위하여, 40℃, 50℃, 60℃, 70℃, 80℃의 다양한 온도 범위에서 일정 시간 방치 후 박테리오파지의 수를 측정하였다. 보다 구체적으로, 박테리오파지 PA4 배양액을 4.0x109 PFU/mL가 되도록 희석한 후 배양액 5 mL을 멸균된 튜브에 분주하고 10분, 30분 및 1시간 동안 각 온도에서 방치하였다. 방치 후 각 반응액을 단계희석하여 소프트 아가 오버레이법에 의한 타이터 측정을 수행한 결과를 도 7에 나타내었다.In order to confirm the thermal stability of bacteriophage PA4, the number of bacteriophages was measured after standing at various temperature ranges of 40 ° C, 50 ° C, 60 ° C, 70 ° C and 80 ° C for a certain time. More specifically, the bacteriophage PA4 culture was diluted to 4.0 x 10 9 PFU / mL, and 5 mL of the culture was dispensed into sterile tubes and left at each temperature for 10 minutes, 30 minutes, and 1 hour. After allowing to stand, each reaction solution was diluted stepwise, and the result of performing a tester measurement by soft agar overlay method is shown in FIG.

도 7에 나타낸 바와 같이, 본 발명의 박테리오파지 PA4는 40-70℃의 범위에서 60분 동안 안정하며, 80℃의 범위에서는 10분 동안 안정하며 30분이 경과한 후에도 어느 정도 안정성을 가지는 것을 확인하였다. 이를 통해 박테리오파지 PA4는 내열성이 우수한 박테리오파지임을 알 수 있다.As shown in Fig. 7, the bacteriophage PA4 of the present invention was stable for 60 minutes in the range of 40-70 DEG C, stable for 10 minutes in the range of 80 DEG C, and stable to some extent after 30 minutes passed. As a result, bacteriophage PA4 is a bacteriophage having excellent heat resistance.

상기 실험으로부터 박테리오파지 PA4는 녹농균, 특히 카르바페넴계 항생제 내성 녹농균에 감염하여 탁월한 용균 활성을 나타내고 물리화학적 자극에 강하다는 장점을 가지고 있음을 확인하였다. 또한 본 발명의 박테리오파지 PA4는 사람, 동물, 식물 등 세균 외의 다른 숙주에는 감염되지 않으므로, 항생제의 오남용으로 인한 항생제 내성균의 문제점, 식품 내의 항생제의 잔류 문제, 광범위한 숙주범위의 문제점을 해결할 수 있는 장점이 있다. 따라서, 본 발명의 박테리오파지 PA4는 녹농균에 의한 감염성 질병의 예방 또는 치료, 항생용 조성물, 사료 첨가용 조성물, 사료, 소독제, 또는 세척제 분야에서 다양하게 사용될 수 있다.From the above experiments, it was confirmed that bacteriophage PA4 has excellent lytic activity by being infected with Pseudomonas aeruginosa, especially carbapenem antibiotic resistant Pseudomonas aeruginosa, and is strong against physicochemical stimuli. In addition, the bacteriophage PA4 of the present invention is not infected with any host other than bacteria such as human, animal, and plant. Therefore, it is possible to solve problems of antibiotic resistant bacteria caused by abuse of antibiotics, residual antibiotics in food, have. Therefore, the bacteriophage PA4 of the present invention can be used variously in the field of prevention or treatment of infectious diseases caused by P. aeruginosa, compositions for antibiosis, composition for feed addition, feed, disinfectant, or detergent.

비록 본 발명이 상기에 언급된 바람직한 실시예로서 설명되었으나, 발명의 요지와 범위로부터 벗어남이 없이 다양한 수정이나 변형을 하는 것이 가능하다. 또한 첨부된 청구 범위는 본 발명의 요지에 속하는 이러한 수정이나 변형을 포함한다.Although the present invention has been described in terms of the preferred embodiments mentioned above, it is possible to make various modifications and variations without departing from the spirit and scope of the invention. It is also to be understood that the appended claims are intended to cover such modifications and changes as fall within the scope of the invention.

이하 본 발명의 박테리오파지 PA4를 포함하는 감염성 질병의 예방 또는 치료용 약학적 조성물의 제제예를 설명하나, 본 발명을 한정하고자 함이 아니고 단지 이를 구체적으로 설명하고자 함이다.Hereinafter, formulation examples of pharmaceutical compositions for the prevention or treatment of infectious diseases including bacteriophage PA4 of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.

제제예 1: 의약품의 제조Formulation Example 1: Preparation of medicines

1.1 주사제의 제조1.1 Manufacture of Injection

박테리오파지 PA4 1.0x107 PFU/mLBacteriophage PA4 1.0 x 10 7 PFU / mL

주사용 멸균 증류수 적량Sterile sterilized water for injection

pH 조절제 적량pH adjuster

통상의 주사제의 제조방법에 따라 1 앰플당(2 mL) 상기의 성분 함량으로 제조한다.(2 mL) per 1 ampoule in accordance with the usual injection preparation method.

1.2 액제의 제조1.2 Manufacture of liquids

박테리오파지 PA4 1.0x107 PFU/mLBacteriophage PA4 1.0 x 10 7 PFU / mL

설탕 20 g20 g of sugar

이성화당 20 g20 g per isomer

레몬향 적량Lemon incense quantity

정제수를 가하여 전체 1,000 mL로 맞추었다. 통상의 액제의 제조방법에 따라 상기의 성분을 혼합한 다음, 갈색병에 충전하고 멸균시켜 액제를 제조한다.Purified water was added and the total volume was adjusted to 1,000 mL. The above components are mixed according to a usual method for producing a liquid agent, and then filled in a brown bottle and sterilized to prepare a liquid agent.

1.3 정제의 제조1.3 Manufacture of tablets

박테리오파지 PA4 1.0x107 PFU/mLBacteriophage PA4 1.0 x 10 7 PFU / mL

옥수수전분 100 mgCorn starch 100 mg

유당 100 mgLactose 100 mg

스테아린산 마그네슘 2 mgMagnesium stearate 2 mg

상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

한국미생물보존센터Korea Microorganism Conservation Center KFCC11697PKFCC11697P 2016102120161021

SEQUENCE LISTING <110> Optipharm.CO.,LTD <120> Novel Pseudomonas aeruginosa specific bacteriophage PA4 and antibacterial composition comprising the same <130> OTP1.29P-1 <150> KR 10-2016-0177044 <151> 2016-12-22 <160> 1 <170> PatentIn version 3.2 <210> 1 <211> 66485 <212> DNA <213> bacteriophage PA4 <400> 1 tcgtcgagct tcctggagtt ccagacgatt tccctttctg aggtaaatat ggctactaag 60 gccgatttgg aattgaaagt tcatcagctt cgacgagtca tcaaatctcg cgagcaagaa 120 cttgaagagt tggaagttcg atcggagcgc catcgcgaac gacggtgctg agcatggatt 180 caagatcaac agcgacattt actaacagca acctggagaa ccaaatggat attcaaaacc 240 tgttcaaact cggcatgaag cgcgacatcg ctcagttgat cgagccggat caccgccgcg 300 cagtaaacct gggcgcaggc aattcgccga ttcccggcgt cgaatcgctc gactggccgg 360 actgggacgg cgccagcggc cgagtgccgt atgaagacgg cgaattgacg gcggtctacg 420 catttcactt cttcgaacat ctcactggag cccaggtcat cgatttggtg aaagacctgc 480 agcgggccat ggcagtcggc gcgacgctca atgtcgttgt tccattctac aactccaaca 540 tcgcccacca agacctggac cataaaacgt tcttcactga agagacatgg cggaccctgt 600 tcagaaatcc gttctacgac aagaacaggg aagacccttg gaagttcatc atcggaacca 660 acgtcatcat cggcgtcgcc gagcggaacc tggcagtcat gtcgcagttg atccgtgtag 720 cctgaccctc tgcgatccga cgaacggtag tgcgaaagtg ctaccgtttt ccatttctgg 780 cgtatagtca acccatcgaa acgaactttc caaacaggag aatcgatatg aacgcagcag 840 agaatctgtt caccggcttc gaagacctgg gtgacgactt cgctaccgta gcgatcaaca 900 acgaagcgcc gaagaccctg gaagacgcgt ccatgggcgc tcgcccgaat tcccggaagg 960 aagtgaagct gtatcgcgac aagtgcacca aatgcgcagg caccggcctg taccgtggcc 1020 cttcgtctta tggtcgcgcc tgcttcgcct gcggcggtgt tggatacaaa gagtacaaaa 1080 ccagcccgga gcagcgcgcc aagagtcgtg ctaaggcggc agaaaagcgc atcgagaaaa 1140 tatgtagcgc tgcgcaagag cgcgacctca aaattaaagc cttcgaagct gcacacccgg 1200 acatcgtcga gtggtggact ggaaattcct tcagcttcgc tcagagcctt caggagtcgt 1260 tgtataaata cggctccttg acagaaaatc agatcgctgc tgcgaagcgc gccatcgaaa 1320 acctcgccaa atatcgcgag aaagtggccg cgcaggaagc tgctgcaccg actctggaca 1380 tttccggcat cgagaaggcg tttgagaagg cgaaagaatc tggcatcaag cgcccgaaaa 1440 tccgcctggc tggcgaaggc gaggagccgc tcatcgttat tgtgaaagag gctagcgctc 1500 acagccggaa cgccggtagc ttgtacgtct tgggcgacat ctacctcggc cggatcacca 1560 atggcaaatt catcaagagt cgcgactgca ccgacactga gcatgacgac gttctgaaga 1620 tgtttgaaaa gccgatggaa tcggcagtcg cctacggccg gaagactggt caatgctcct 1680 gctgcggtcg cgagttgacc aaccacgcat ccatcgaaat gggcattgga ccgatctgtg 1740 ccggaaagtt cttcggatga tctacataac catcaaagcc atggcctggt tcgccctcct 1800 atgggcgacc ggcttggcca tcgtaactct caccatacat ttatgctact gaggattatc 1860 catgagcacc gtccatgacc cgatgaagga caagatcacg ctgcacggcc tggggttcat 1920 tcaagtccag ctcccggcag ggcgcctcca tgtttggcac ccggagttgc cgcgccggct 1980 ttgcttcaat cactcggcca tccacgatca tagattcgat ttcgagtctc tggtactggt 2040 tggatcgatg gagaacatca actattacga ggatcgctcg gcttgcctcg gcgaaatgac 2100 tcacgaaggt tatgaacact cttcggctcg ccaggcttgc ggcggtcgcg gctggaatcc 2160 tgtgggctct gtatgtctgc gccagaggca aagatttgtt gttgacgccg ggcagcaata 2220 ttctatgtct gcgtacgttc cgcacaagac gaatccgctc ggtgacggcc gcgtggcgac 2280 tctcatgcgg aaaggcagcg ttcataaatg gcctgccact tcctatgtga cgctgggcgt 2340 cgatcccgaa accgacttcg accgctacca gtggtcggtg ccgacgctct gggaagtcgt 2400 caccgatgtc ctcggcggcg cagagttcca aatcccatcc atcccttgac cgaaggaacc 2460 aaaaaaatga agaaattctg tatcgacatc accaatggcc tggccggctt catcatctgg 2520 ggcggcgcca tcgtcctggc cgcttctgtc tttctcatcg gtccgctggc catccttctg 2580 accggagcct gggttgtgtg tacgtccgtc gtgttcgccc tctggttcgc cgtcgccggc 2640 atctacgaag agtcgcaaaa gcagaccgag catctgaaat ccctggtgtc gctccaggcg 2700 cgtgaacgcg gcatcggcta cggtccagga gatgccgttt gcagcgccag cgctccggcc 2760 gttcccgtag agcccaagct cagccatccc aagctgaagc cgggcgcaca gctcgcggcc 2820 gccgtcttgt tcttcgccgc tctcatcctc ctgctggtag caggcgattg gatctggaat 2880 ttcttccagt caatgccgaa atagtggaag aaaatgcttt acttccattc tgaatgaagg 2940 caaaatagct ccattgaaac gcgaaaccct tcagacaaaa ggaaccgacc atgaccgacc 3000 agaacgaatt caccccggaa gccatcgaga aggcgaaaga ccgcatccgc aaactgactg 3060 ccatggcggc cgactcctcc agcccgcacg aagccgccat tgcagccgag cgtgtgaaga 3120 agctgaagga caaatatgac cttcacgact tcgaagtgac cggcgagatt cgcgaagagt 3180 tcgatgagca gatcgcgact cgttactatt ccgcaatccc gaactggatg aagttcttct 3240 cggtggccgt ggcgacgtac aacgactgca tcatggattt cgccggtggc atcaacgatc 3300 accgagcgac cgccaaggct tcttggcacg ccgcaaacgg cgggactacg aagcgctggg 3360 gtcatgccgt ccgctttaaa ggctacaaat cggacgttga gctggcggtg aacatgttca 3420 actcccttgt cgaagcggtt gatcgtctgt gccgggagta tcagaaggct caaggatacg 3480 gacgattcaa cgtcaaggtt gccgcgcaat tcaagctggc cgcgacccag gaaatcagct 3540 atcgccttca ggccatcacc aggaagcgca tggagctggt atcttctgcc ggaacgtctc 3600 tggttgtggt gaaggaagct gcggtgcacg aacatttcgg cgatcctggc tacaagaagt 3660 caaatgttac caagctcatg cgcctggacg atagcgacgg tcggcgcgcc ttcaatgccg 3720 ggaccaatgc cgggcgcaac ctggaaatcg ttcggtctgt ggaggattga tcatgagctt 3780 ccctagcgac aaagttatgc tgcgaatcgt ccaatccatc ctcgcgatcc tcatcgggat 3840 cgcttgggcc tgcgccgact atggagtcgt ggccgccgaa cttcctccat cgctgcaggc 3900 ccatcccgcg aggccagggc acagcgaagt ctcggcccgc gaccctaggt cggtcgaggc 3960 cgaaaaagcg cgggaagagg ccttagaata tgtcctgtcg ctgcgcccgg aagttatcga 4020 ggcgaaagct cgtttcgcgg ccgaggcggc gcagcaaggg ctgtcaacca aggagtacgc 4080 tgagctgcag agccgaacca aaatactcac aggaacgcta ttggcgtttg cagccttctt 4140 gttcatcttc agcatcatgc tacccaggct ttgaataggc ctgggtagac cacaaacccc 4200 cagccaaaag agaattacca tgaagaaaga accgattcgc ctcaactcca tggcctcggc 4260 ccgatccatc gatgcggaat tcgcattccg gatggacgag ttcatggctc gtgtagcgaa 4320 agagcacgaa gcgctcgcag ctcgcctgaa tgccgagcat gtggcgctct gggacgaaat 4380 ccgcgctgtc gccggcctga gcgctgccga cttcccgaac atcgccatgg cgcacgacac 4440 ttccgatggg aagctctatg tcatggatgc cgacgagttg gagcgcgtcc gccaagcctg 4500 tccctgcccg gactgtgaag ccgctcgcgc tgaaagcatg ccgtcgcaag ccagtggagg 4560 gattcattga tggtactgaa gctatcttcc gttcacgttc ggatcgacgg gcctgatggc 4620 aaggtattgt cggaaggcca cgcagagttc tccggaacgg cattctggat cgccgcgcaa 4680 cgcgaaatgc agctcaagca tcttgtcgga acttccttcg aaggcgccct gacctacctg 4740 gccgacaatg gctacaacgt aacattcagc aaaggtgaaa agcgatgatc gaaagacatg 4800 tagtggatgc ggaagtggtc gagcggattc gttctcttcg catgcgattc aacgtcctgg 4860 acgaaaccct gcaacgggcc gtcgatatgg cgatgctcag ccaccagaaa tctctgcaag 4920 acctgcgcaa ctatgaagct cagctctggg atgcgctcaa tgcccgttac ggactgtccg 4980 tcgaaaagac ttatgacctg cggttcgaag gcgaagaagc cgtgctggtc gaggttccgc 5040 caggcgacgg ccaaggtgat gacttcatcg tcgagtcgga agccgaagcg ctcgcggccg 5100 gccaggaagc cctgggagtc ggcgaggccg ttgcgtcgac actcagcgcc aggaaccaca 5160 ccgagtaaga cccgaagccc ggagcgatcc gggcttttct atgtttagaa gtcgaagaag 5220 cctttgggct tccggatcgg cagaatggcc gacataatca ccgagtcagc gatgttcggc 5280 gacttgatct tgcgtttctc gcgcatatcc ttcttggact cgactttgaa ccggccgttc 5340 atgtccaggt ctttgcgcgg cgacgaaagt tcgatacaca gttgatttag tttgtccggg 5400 tgaatcgttt cagagttgat cgaaatcaat tcgtcgaagg gataaacctt tccatgctca 5460 accgcttcat aagtcttccg gaatcgggtc gcgacttctt cccacttctg cgccttgatg 5520 ttgctgaagt ggtctttgtt cttgatcgtc gtgtgcggca gcttcatgta gatatcatca 5580 ggcttatcga cagcgccgcc cgcgttgaat ggatcataga tcagtttgaa gtcgggactg 5640 gcatcgttca actcggcgaa cttcgatccg acgtgagcgc cgacaccgat ggagtcataa 5700 gtgaccgagg cgcctttcat cttcgccagg ttgtaaacgc ggctggacga cttgagcagt 5760 tcatcttcca ggccgtccca ttcgtccact tccataatga cgttgccgtg catgagcgta 5820 gttgcgttcg catcctcgcc gtcgtccgca acgtcgaagc cgatgcgctt cgatccggcc 5880 ggctcccagc cgagtttctt gtgggcgtcg atggccgcga gaatgaactt gaggttgatg 5940 acggatttgt cgcctccagt cttcggaatc cctccataaa tgtgctcggc ctgctcccgg 6000 tcgcgctcat aggcttcgtg aatcactttg agcatcgtct cactgaggaa cggattttca 6060 ttccagttga tcatcttgac gcatgagtct ttcgggggtt tgaccacgaa gttctgatac 6120 acgaaatcgg tcacttcgtt cgggttgaag atgatccaga tttcagagtt ttctttccgg 6180 atggtaggct cgatgacttc ccattgttcc tgggtcaggt agtgagcttc ctcaagccag 6240 agaatgtcga tgccttcggt ggacttgatt tccgacaggt tacgggcgat cccatagaat 6300 aagaattctg atcctgtcct cttgtgcttg atcgagttct tcgtgaaaat gaactcgccg 6360 ttgtactcag aattctcaat cttgtccttg atcaacgtgt agaccgattc actgatgcgg 6420 ttctggaact ggcgagcaca gaggaacttg agtctatagt tggccgcgag gtaaacggcg 6480 ataccgcctg cgtcgtgtga cttcgaagac gcccggccgc cataaatgac tttgtaacgg 6540 gcgcgagttc gccagaccgc tcgcagtgca ggattgagtt tgtacattta atcagtccat 6600 tgttcgcaat aggccgagta tatcgacacc gcagcagacg gtcgagcaca accgttcgtc 6660 ggtgtgcaga atttttctca ctcagacact ttacttccat tctgactatc ggcataatct 6720 cctcatcgaa acgcgaaacc cttcaaacaa aaggaagccg aaaatgacta agcaagccaa 6780 aatcctgagc gtcgctaaat tggccgtggt cactgaagaa gtcgccaaag catacctgga 6840 agctgaagag tggctggttg acgaagccgt gtacaccatc aaggctgagc gcaaagccgg 6900 cctgctgtaa cggaatcacc cgcccggttt gccgggctga cagccctgga gggtaaaacg 6960 atgatccaca ccgtgaacgg caagcagtac atgtacggca gcttttccgg cataaactcc 7020 aaactttacc gcctggaaat tcgccacggc ttcaccatgc cggtgcaggt cgaggtccgc 7080 aaaaacagcg ctgaatacaa gcgtgtttgc ctggccatca ctactggcgc ctaaccgacc 7140 cgcgcccggc gaaccgggct ccaaaactcc aaaaacagag gatcgcagaa atgaccaaac 7200 aagtccagat cgaagtcgcc aacctcgatg aagctttcgt ccagcacctc ctggcaggcg 7260 gccatctgtt cgatgtcgac gactatgaag ttgcagaccg catcctgctg aatgtggatg 7320 gcgaaccggc tatccagttc gaactgaatg ccgaactgtg gaacgaagag actctgggca 7380 ttccgatgga catcgacagt gacgagttcg ccgatgagct gcaggattgg gtcgagtcga 7440 aggtgaattt cgccttcgaa gagtggctga gcgcggacga aggcgaagag tgattacgat 7500 gcggctggga tggtcccggc cgcgacttct tatgaggatt gtgttatgtc tagcatagtg 7560 tacttccagt acatcaccgg caccattcag gttcctctgg aagtcgaggt ggaggccggc 7620 cagctgcaaa tggtcaatgt agaagtcgat cctgatggct tccgcaaatt ctggcctatt 7680 gccgatagtc tgctatggga cgcagaggag tgcaagtttc tgcctcgcta caaatccaac 7740 tacatgggtg aggccgtaaa gtatgccgac caggctatgc tcgctttcgc ggccggccaa 7800 tactacctgc ggatggggtc gaaggaagag cgtaaagacc cggacgccga tctgcatgcg 7860 ctggagttgt ccgcattgcg agcagaactg cgaaggacca aagtcgccaa acagcagctg 7920 gtgcgcgaaa atactcgtct tgtcgaccgc ctgcagaact tcgtagcccg cgaagacaag 7980 gtcgccgagc agaaccgcca gcttcaactc agaatccagg atttggaggc cgagctagcg 8040 tcgcagaagg ctcttcggga agagttagac aagagcctgg acggcagcat ccagaacgcc 8100 aacaatcagc acaagctggc gtgcgaagcc agggagcaga tggtcaaggc cagggaagag 8160 gccgaattct atcgcatcgg catgcagaaa gtcgcggcca tagccaacat gaatcctttc 8220 gaggactact gaccgtgcaa aagtacaacc tgtcccatat ccctcgccca ggaacgctcc 8280 agttcgaatt cgaatggctc gccgttaccc ggttcggcat caaggatggt gctctggcta 8340 tgtcgtccga tggcgagcgt tactgcaacg aacacatcga ctggctctgg cggcagttcc 8400 tgacttcaaa aggtttcaga taatctgaag aaaatgcttt actcaatgag gtgacttagg 8460 tatagtcacc tcattgaaac ggaacaatct cggagagaaa gcgatgccgg tatttaacat 8520 tgaccagtcc gtaactgtag aagctgaagt agaaaagggc tgtatctctc gcattgccca 8580 tctgtgggac gaagagggga atgatctttc ctgcaaactc ggcgcaaccc gagctttgaa 8640 tgtcaaagcc gcctgtgctt atcttgttcg cgatcctgcc gctaaggaag tgactactga 8700 atgcggcgta acaatccgtc gcggcaaagc ctaatccaac gcgcccgatt ctccgggtat 8760 caccgaggaa cgaaacaatg atcggcaccg tacacaaaga atccccgctc accttaagca 8820 cccgcatcgg ctccgcatcc ggcgagaaac atacctacac aatgctggtg ggcgagccgc 8880 tgcggactcc cattatcatt cgtgatgacg gcaaagcctt caccttgacc tggccagaga 8940 tcatcaacct ggcgcgctcg gcgttcgcta tcgatgacgc ggccgattga tttgtcttcc 9000 agaaatttta gacaatctgt tcaaaagtgc tttactcgat gatgtgactg agatatagtt 9060 acctcatcga aacgcgaaac actccaaaaa gaggattgcg acatgactag ctccaagtgg 9120 accatcggca gaaacgacac catcgaagtc gaggccgtaa acagccgcga agatttccgc 9180 tggaatggca aggttcgcgt catccactac agcgccggtc aaatcgtcaa catcatcgag 9240 ttctatcacc acgatctgga ctgggcgatc aagaatttcg gtatcaagct gaaggctatc 9300 tccaagggca tggaaatcct ccacacctgc tacttcggga agtatgtcaa atgatcgtcc 9360 aactcgactc ccaagaagag aaaatcatcg gcctgagaac tctgtccaag tatcgtcgcg 9420 ccggtggcaa gttcgcaccg gtggacggaa ctcagaccgg tccctggggt ccagtcgaca 9480 acgcgctttg ggcgaagctc gaagccgaag ccagggcaga atacatccgc aaacaggagc 9540 gtaaagcatg atcaagcaag acctgtacaa gcagatcgcc ttcgaggcga ttggctccgg 9600 catcaagatg ttcgtcaagc tttactgcaa cgacaccatc ctggaagtca tcggcgtcga 9660 ggaggcccac attgatggga cgactcggct gcgttacacc ggccacgccg atggtgtcga 9720 tgtccatttc ttcatcaatg aaatcgacat ggtgatggta tgagtggcca ttctatgttc 9780 gactttgaag tcgatttcaa tagcgccacc aatagcgcca ccatggagat cgatcccggc 9840 tcattctatg taggcttcgg gtttggtgcg actgctctgt cagtcctgat ttatgtagat 9900 ggagtatggg tgagcgaacg gacggcatgg attccagatc caaaagagat atcgccatga 9960 gcaagcgcaa aaacgatcaa ggcggctggg cgcagcccgg caatgctcgc aaagtccact 10020 tcttcgcggc ggacggccgc agtctgtgca agcgctggct gtatctcggc aagacttaca 10080 gcgagctgcc cgacctggaa atcacctgcg cgatctgcga gaagaagcgc cagagtcctt 10140 tcgaggaata ctgcgacacc attctctaac gttcaagcct tcaaaaaccg aggaaccgcc 10200 atgaaactct accatgcaaa agtcagccct ccatccttct atcgccacaa ccagaccgac 10260 gaagagcgga aagccttgga ggcggaatat gtcagcaagc tccacgttct cctggggaac 10320 ctggaaggcg taacaatcgg gaatcctggt gagcggaact gggagccgtc caactggagc 10380 aacgacgttc ccgtgatgtg taatgaaatc ggcctgggcc gtctgaccgc ttcagcctgg 10440 gatctggaca aggactatcc gtacaccatc atcaacctgg tccttctctg ggacgacgtt 10500 gacccggaag ccgctctgcg acccatgctg gagcgtctgg agctggccgc gagccggttg 10560 gccggtatgt cagtaagcta catcaaccaa ccggagatgg tgagtggaat cgagggttgg 10620 aactcgctca caggatctgc catccctggt ccgaatctcc agagcataaa tcgtctccta 10680 ctcaaggaag actgctgcac ggatgaactc cagtccgccc tggacgcagg atggcgcctt 10740 ctcgccgttt gtccgcagga agcgcgccgg cccgactaca tcctgggccg attcgattct 10800 gtcccgccga ccggaccgcg tggcgcggcc aggagcatcg attaaatgac catggtaggc 10860 ccggctggaa agcgctactg gcttcggtat gaaaccagat actgggagtg tcttgacgga 10920 caaaccctgc ggctggtctt cgtcatcaac ggtcgccggt atgaggtcaa tcgacgagtg 10980 aatgtagaca tcctgtccag tcggcgcagg ttcgaatctt tcggccgagt cctggcaagg 11040 atggaaatca gcctgtggtt cgcagtgtgc gagcaagaag ggccatggcg cggtagcgta 11100 gccataagcg ataccgcact ttggttccac ctgacgggag aattggtaca caaatgcttt 11160 actcggcggt gagaatcagg gcataatctc ttcaccggct gagaagccgg acccgaagtc 11220 caaaaaggaa tctcgaaatg tacagaactc cctcgtccaa attcacgttc atttgcaacg 11280 gcctcgccca gaatacagaa gtgacggtcc tgctccggac gcagaagccg gaagatgtat 11340 gggtggtgga cgaagcttca gttgcgaacc tgattcgcat ccatgaacgc agcaatccgc 11400 gccgtcgccg taccatcagc atcctcgacg tggatgcagt gtccatcctt cacaaacgtt 11460 aatccatcgg cgcggctgga ttggtcccgg ccgcgccatt catgcaggag tgtattatgg 11520 ccaaaatatt gatggcctgt gagttgctcg tcggcgacga aatactcact catgttgacg 11580 tcaacgatcc cgttcggcgt cgggccatag tcctgcgatc tggagctgcg ccgcacagca 11640 aagtaagcat cgaagtctcg gcactcatcg gcgctgactg ggtggacttc aagctcaagt 11700 tggccaggga ctatcctacc atctgcttac atgacatcga cccgatccgc cctcgcggcg 11760 ctgcccaata ggagaacaca atggcaaaag ttgtaagagt tgatgagttg aaaactggcg 11820 atgaaattct gattaagctc agggcggatt ccgcagccag gaacaaggca attgtccttt 11880 ctgtcgaatg ctggcgcgac gaaatcaccc tggagcttac ctgcccggcc ggcgactact 11940 gggaagactg gcgcggtaaa tatcgcgcat atgacaaagt cgttctgttg aagcgcgact 12000 aacaacaacc agcctctgcg actcggcaga ggctttctca ttggagggca gcttatgtcc 12060 gataaagaac aaagtggcca ttactgggtg acggtcagtc cgaccgatct gtccagcgcg 12120 tcggccgcgc agcgactctg cgaaacgatc cgtctgagca tgacgcgagg cgtcgcagcc 12180 tacagcaagt tctacggctc gaaaggtgag tgcctggtga cgcgagtcat tccgcaccag 12240 tgcgaactat tcgtcaatga cgagtcgggc acgaatcggc gtcgaacggc gatgatgatc 12300 gaatacgtcc gcttcaaagt tccggccggt atgtctctgg tcgaacacca aaagcaacct 12360 tactgagggc gcaccatgct atacatctgg gaagatcaag acatccacca caacatcgaa 12420 actctggctt tcgtcggcga gtccaggtcc aactacacaa tcatcggatt cgaattcggt 12480 gatctgttcg ccatcgccaa agagtccact ggtcagatcg tggtaagcct gctgactcgg 12540 caagggatgg cggaatggct taccatgaac ggccatattc ctgccgagat catcagccac 12600 ggacccggca accacaaaaa cccgtatgta tgggcggact ccatcatcct gaacaatctg 12660 ccgacccatc cgaacatgcg ctgcgttacc actccattca cgggcttcga tccagcagaa 12720 ccgggtggcg acaagactgc cataggtcaa gtcatcaagg acaaccgatc cgccgaaatg 12780 ttcggcgaca atccgtcgca gcggtcgcag cggtcctttg gcggcatagc gccgagtctt 12840 cctgatctgc ccgatcttcc ggagccgccc agggcgccga tggctcctcc aggcctaccg 12900 gttccgcccg cgcctcatgc gccaaaagcg cctccagctc cgcaggtaag caggcagtcg 12960 gaatcgctgg cgcttcggtc gggtgcgatc ccttccagcc cggcgcccgc atcggacaac 13020 gacaggcccg gcgatccgcc catcgagcct atcacagtcc cgactttctg acatcacccc 13080 aacgccaaca aacaccgcag cctgctctgc ggtgttttca catccgacaa ccgttcgtcg 13140 gctttgcgat caatctgatg aaataaatgt agacacgcag catcgaccta ggcataatct 13200 ctttcaacgg ggcgacaaac cgaagcccga acgaaatctt ccaaaacaga ggatcgcaaa 13260 atgaccaact ccatcaaaac cttcggcgac atccagaacg cagaaatgaa agaactggtc 13320 gccttctaca acgcccacaa cgccgatgcg actgtcaagc gcttctctga ccgcaagacc 13380 gctgagcgtc gctgcctcgc catcctgaac gctctgccgg ccgaggaaga ggccttccag 13440 gaagaggaaa ccccggccaa ggtttacaaa acccgcactt ccaagaagaa ggcagaagag 13500 aaggccgaag agaatctgaa gccggaagaa gaaatcaccg aagaggaagc gctggaagaa 13560 atccggaaaa tgcgcgaaga ggcgaagaac gcgccggaga aaaccaaaga gaccaaagac 13620 ctgtcagcag ccatcgccaa ctcctggaaa gacccggaag tcgcccgcaa gcgcaccgag 13680 cgtcatggcg tggcggtcac cgtgaaaggc aagcgcggcg agttcaaatc ctgcaacgca 13740 gccttcatcg agttcggttt gccttcctct aagtgcatcc gattccgcat gcagctgaaa 13800 gcgtccggca aattgacttt cgagcacgaa ggcgtcaaat acaacttcga aatcatcgaa 13860 gctggagaat aagaaaccca aaagaaagcc ccggattctg aactagagtc cgggggcttt 13920 gtcgcttctg atcgttattg gtcggcttcc tagaacagcc ctagaatcgt ttttcgtccc 13980 ttcccgctac cttcgcctta gttcggtccg attcgggcct agaacgatgt tattttatgt 14040 ctaaatgggg ttggcgcggt cttcctcggt cggttccgga gacggagacg ggaaatctcc 14100 ctcttcacct tccggcacat agccattggc ttcggccgca gcagcgacgg tcgcggtctg 14160 agcctcggct tctgatgcgt agaaatcggc caaaccgcga ccgatccggg tcttgcccga 14220 ctcgtccacg aacgtgattt cagccagaac gttcaattcc ttgatggccg acagacggct 14280 ggagtccttg acggtggggt cacgaaccat ttggaggagt tcgtggagcg ccgtctttgg 14340 attccacaaa tcggacgttt tggtcgcgtt caacttggcc ttgaactgct tgcgatagta 14400 cgggttggac tccatcgcga agatgcgggc ctgcgcggga ccgtccatat gctcctcgcc 14460 ccagatggcc cggaagaccc gccaggagct gtaaccttgg acgcgcaggt cgatgtacag 14520 gtcgaatcgc ttttggttga tcgccgcgaa atgcgggtct gcgaattcct gtggcgtgac 14580 tagatcgtcg gggctgtaga atttggtcat ttggtgctgc gtccctgagt tcgattctgg 14640 agtcgtcgcg gtggctcggt tggtggatgg ggcctggtgc tctgtcgcga cactgagtat 14700 ggcgcgattg tactatgggg ccagggatcg cgtctatggg ctgcttgtgg gtgggctgta 14760 ggtctgggtg ggtttgatga tgaatgagtg ttaggtggtg ttataggatg ttatacgggc 14820 gatccgctgg tgggtgagga tcgagtcggc ggtggcggga gacgatggtg gtgagtgttt 14880 ggattgagtg ttaaatcgaa tgttagaaat atgtccagct gagcgattct gtcgcgctcc 14940 caaatttccg gttccgttcg tcgagttttg gcacttgccg cttagtccgc cgtggtgttg 15000 ccgcgaccca tggattggaa gtccggaagt ttccggcgac cctgccgcga gctggctgga 15060 atcggaaact tgacgggata tgtacaagct tagtgccgcg aggctttcaa atactaaagt 15120 ttaccaaatt accaaattac tattaattta attaatttta aagataggta acgtccgtga 15180 tagatttttt ctattaggat tgtgcaatcg attttcgctg tagaatagtt ttaacccatg 15240 ctcgaaaaac cggaaattag gaaattggcc cgctaaccca cgcggcagta ggcttcccaa 15300 attaccgctc agaatcgcta tacagtaatt tgcggctagt tcccacggaa agtccacctc 15360 aaacacgcaa tttctcaaca tttcacgcaa aatccatcca ccatacacgc taaaccgata 15420 ccgaaaatct atcgactttc cattattcgc gctcgaaact ggtccaaatt actgtattca 15480 cttctaccaa tcccgcccaa cgccggaatc taatgtacgc cgcaccaaag aaaagaccgc 15540 ccgaaggcgg cctagtccaa gtacactcaa ccactacatc agaaatcctc gcccaaaatc 15600 ttggctcgct cggcccggac tgcccgaatc tttgccatgg cggcctcatc agtgatatcc 15660 gggtcgccct tcctcagcaa gtacacaagc gcatcattga acggcggcag cgtggtttgc 15720 atactattcg tccatccagg tgcaacctta tcgacgggca ggcaccaacc agccaggccg 15780 ttcttgttcg ggacgaaccc cagcgccttc aggtgcggag ttaagtggcg agaaatcggc 15840 ttcttcctgg cgagaatatc gaaccatttc agaatggtga cggtgtcagc cctccaccca 15900 ggattcttgg aattcttgcc cggcttgatc tcttcgaact cgcaacttat cagaacgttg 15960 atcagataca tgtcaatcgt atcatcacga accacgccac gcgcattctc catttccgaa 16020 atagagaagt tctgcacttc gcggttagct tccgacacca tattcaggta tccatcgacg 16080 ccatgctctt cgatccaggc gcggcactca gccatagcct gccagaactt gcggccgaag 16140 tctgtgaagt ccaccttgaa cggttcatta ccatcgcccg gcttaaccca gttcggcttt 16200 ccatcttcgt cgggaagttg tgccacgaac atcggataga atcgacggtt gccggagtcg 16260 tcccgctgga gtccatcgta tccgttgccg tccatgatgg tgatccattg tcgcttgatc 16320 gtttcgcccg gctcgaattt ttgatcgaat gtatccgaag atcgcaccag gaattctttg 16380 atgcgttcca tgtcgccctt tttgaagccg gacatttccc cgacgttcgc aataaccgag 16440 ttgccggtga tgttgcgcag gaacggcgtc tggtcgtgtc ggctcaggtc gagctgaact 16500 ggagctagat cgcgcccacc ggacagttcc ttacagatca gcaagccgaa atatgatttc 16560 cccgcatcct gcccaccaat caacgccaac gagatcggcg ccgaaattcc cggatagttg 16620 atgcggcagt acaggctcag ccagaaatac ttgctcacca tacggttgag ctcggtgtcg 16680 aacggcttga aaagatcgat cagcaacgtg ctaattcgct cttcgccgtc ccaatccggt 16740 atcttcttct caaacgtctc gatcaaagag ttgcggcgat atcgacgcgc ccaaacgcag 16800 caagtctcaa tcgtcttctt aatcgatgga tcgtccaagg ccgcagccgc gagggcgccc 16860 atcaggtcaa tggggtcgag ggtcttgttg ttgaacgcca cgcctcggtg gtccaccagc 16920 cggccgcgaa actcgtcgaa gtgcgggtgt gggacggttc cgtcgccctt acagaacaac 16980 gtatcataga ccgcgaggta gttgctgtct gacgtcgagc tgtatttcgt gatgaagtca 17040 tcgaacggcc ctttcaccac ccggctgacc ggaagatcga acgcctggtc gagcatcaac 17100 aaccgcgctc gcttcctcaa gtctggttca gcatacgcct cggcgtatct tgccgccttt 17160 tgcgcgcgat gcgtttcgtt cctcgcaatc gcatcatcgg ccgccttgct cgcggcggtc 17220 atcaaagggt ccattccagc atcttctatc tgcgtgagat caaactcact ggaccctgat 17280 tcgccatcat caaaaatatt atcttcgtcg ataatcatgt taggtttgcc gccttctgct 17340 ttacatgatc ggattcaaca ttgcctctac acattgaggc gaaagggacg gctattatct 17400 cctacctaaa ccggcatagc taataagttc cgtccccatc cgaaaatttc tgtaccgttc 17460 gtcgattaaa atacgtcaaa cgcaacgacg aaccagaacg tcaaagcaga aaggccgaag 17520 aagaagcaca gaagcgacgc gaggaagttt gcgacttgta ttttccatcc ctttaggcct 17580 tcgaagaaga tgataaggcc gaggaacagc aagccgatgg cggtaatcag gattccatga 17640 tcgttttgca tattgtctac tcctcaccga tatgacggcg gttgattctt tccaattgtt 17700 cgatgatata gggtagcacg acttcatccg tgaaggccgc ccaagtccgg cgatgctctt 17760 tgcggcaagt atcgtgcccg caaccgaaca catattcgtg ctcggcgcca ggtatcggtc 17820 cgcgaaagta tgctccgaaa ggatcgccgt tggtgtgctc gtcgccccat ggacagcgga 17880 tgcggtattt gccggacata ttctgctgga cctggccgcc tgccgcttcg cccatcttgt 17940 atttcgtgca gatgtgctcg gcatacttca gccatacttg gtcatacacc caatcgtcgc 18000 ggtttatctc caccttcttc atctgtggca tgatgatgcg gacgccaaag gccttggcga 18060 tctcttccgg cgagtagcgc ttggaatagt cggcgctgta caggcgcacg agttcgggct 18120 tgccgttttc gtcggcatat ttgaacttgc cgtctttccc gcgcttgtta ttgaagccga 18180 agggcattcg gccgtaacgg ctgacgtcct tgactgtgtt gtcgccgcct ttctttagca 18240 cctggtccac gaacgaatag agcagcgcct tgaactggag catgtgggac atcggctctt 18300 tgaagaaata ccagaactgg tagttgttcg gcgaagtctc cacaatcgcg gtcggctcta 18360 gtcgctcgcg gaactcgtcg cggtcgaagt cgcctttgga ccctttgccg gagccgatgt 18420 catcgaccat caacgccagg ccgtggccga aagaggcttc gccgcgccag taccgcatct 18480 ggcccgtctt cgggttgggc gtcttgatgg acgacgatat acaggcgtag gcgttggatc 18540 gggagttgat gtatttccct tccttccagg gcacaggcca ccagccggcg ttgagcttgc 18600 ggccgttctc gtcggtctgg actgtggctt cttcagcgta gccgaccatc acccgttcgt 18660 cgtccggaat ccctctgccg agttctcgca ggaattcttc ggcctgagcc agtcttattt 18720 cgtgaggctt catgcaagtc gctccggtct tcctttgcgg cgaggtactc caacgaactg 18780 tcgcgcagca ctcgcctttc tggcggagtt taggccatct tcatggattc gactccaggc 18840 ttccatgatc ttgtgctgtc tcgccttttc gagcgccggg ggaatcttcg catcgtcgat 18900 gccgcgcacc cacatgaaca tcaggaacgt cgccaggtcc aggaggttgt tctcatttcc 18960 cttcagcgca tgttcggcga atccgttgat cagaacgtct tcgtcgcagt cgatccagcc 19020 gcctcggcct ttatcgcggg agcgctgtag tttctggcgg atcgctgctg cgaacatgga 19080 cacggcgcac tcgtcctgcg cttctggctt cgcctttcga agaatgcgaa tgtcgagatc 19140 ggtcatggcg atggctccat ctacttccga aggtttctgc tgttccatta catgaactcc 19200 ttgcttggca cttaccgctc gcacccgcag cgggcaggat gggcctgtgg ttgctggcac 19260 ggctgaggat gcgcggccgg atcgatgggt gagggcgcta cgtcgagcat ttgccggtaa 19320 atctcgccga tgctgtttgc cgcgtcataa cgcagggact gaccgacaga ggtcatctgt 19380 gatgtcgggt ccatcggtac gagcttccac ccctccggca cgctgggttg agccttggcg 19440 accgctagcg cctcgttgag ccggaaccct tcgtgcaccc agtccgtcaa cttcccttcc 19500 agctccgcga ccctggccaa ggcggcgtcg agtcgttttg cattctcgtc gcgctcgtac 19560 atcatcttca tacacctgtc gaagctgcca gagggatcgc cttttgattc tcgcaggcgc 19620 tcgacttcgg ccaaggcggc gtcgcgttcc actttataac gacaataagg atggccgtat 19680 tcatcgccga ctacgccgtc acaatagctc gcggccagct cgctcccgcg cttttcggat 19740 tcgtccaact tcttctccag cagcgaaatc gtctccagag catcatagag tttgttggcg 19800 tcggtcttct caaactcagg gatgcttggg cgattttcgc tttgttcttt ttccatatta 19860 ttccccagca ctcccaggat tcgccttctg ccggcatcag ttatgttcca gcaaggttgg 19920 cgaccgaaca tatatccagc cacggaatcc ttccatgata gctcgacaag cccctttcgt 19980 ctcaaagcct taagagtcaa attcgttggc gatctgtgaa ctggatgctc aggatgcctg 20040 tacatttcca gtagaacggc atgctgccga ggactcagct ttggactcag ctttcccaaa 20100 tcttccatat cattcacctc aattacagat ggcgatgttg agaactttat cgcgcccggc 20160 cgcgaacttc tccaggaagt ccaccaggtc attcaggatg gtccccgctc gacctagctt 20220 gtggccgatc aggagctgcg cgactcggtg tccgacgaat ttccccgaag gaattttcgg 20280 ccatgtttcg ccgatgcttt tgagtactgc atcagtgtag tctttgtccg cgccgacttt 20340 gtggtgatcg aggatcgtgc gatcacgaac gtatcgattg atgatccgcc gcaggaactc 20400 gtcttcagtc ccggccaggg cgccgcactc gcggagctgg cgcaggagac gccatccaag 20460 gttccgctcc cacttttcag agaactcttc ggcttcggcg aatgacgctc gcatgatgtg 20520 atcgaccggg atgatgacgg cgccgccttc tttcgttccg gcttccatga ccgcccattc 20580 gccatgctcg cggtgctcga tgaagccgat cagcatgccg atgaaagctc catcttccgg 20640 aactccggtc acgcgaacta cagaatggcg cgggaaggct ttcgatccat aaaggctgga 20700 ctgtgaattg acccatccgg ccttggccaa gtcggacgct tcggcgtgga tcagctcgcg 20760 acgaatgcga actgccagcg ccgggtccag ctcgcggctg cggcgcagga aaccgggctt 20820 caggttcggg tcgcgggtct tgtcgacatt gggattcgga ttaccgaccg ggagttggtc 20880 gcgggaaatc ttgcattctt gcatttagtg tatcctctgt tttggagggc agtacaggcg 20940 gcggcgctag tatcggccac tttcctgccg aagtaaagtt ggattaaatt cgctcgcttt 21000 ggcgagtcag ctgatagtat actcttcctg cgcagaggta aagcataact gtacgttata 21060 aaggaacatt cgatggcgga acatattttt actcacgaag gcacggtggt gttcgagggg 21120 cgatcccgaa cggtcaagct ccggcgcggc aaccaccact gggtagactt cgatagacat 21180 cgctatagcc cacaggacgg ccgcgccgct tcccaggcta ttaagggtgc ggtcctggtc 21240 ctttcgaccg tccgctggct ccctggggcc aaagaggccg cagagcaggc gaaggctttc 21300 ccgtataaag gaagggtcca cgcgcttgga gccgcttggc attatgttct gctgcggcgc 21360 acgaagaact tctatgtcga tccgcaaggc cgcaagtatc gtcgtgacac tggatggtct 21420 gtggacggcg tgcttaaact gagcctcgat tcaattaaac ctagcgttgg agaacgcaaa 21480 tatgtcagca tctaacttca ccgtcgatca gatcgaagag cgattcggct ttcgaccaaa 21540 cagtcagcag atcgacgcga tcaattccgt tgtggactgg tatcgcggtt ggtgtgatcg 21600 agcgcaccgc cgccaggtct atcgactcgc tggtttcgcc ggaactggta agacttccat 21660 cgcgaagatc atcgccgaac tttgctgctc gatggactgg acagtcttcg tcgcgccaac 21720 cgggaaagca gcagcgcggc ttcgcgagaa gggttgcacc aatgcccgga ccctccacag 21780 cttcatctat cggccgattg gtgaagatga agacggcgaa atcatgtttg ccaacaaaga 21840 ctcgctcgac gagaagccga agttggtcgt gctcgacgag tcgtccatga tcggcgagtg 21900 ggatgaagag cgcttgctgt cgcaccggat tccggttctg gagattggtg actttggcca 21960 agttcctcct gtgcgcggcg tccagatttt ccatgagaac agctgtgaca ccatcatgac 22020 cgaaatcgag cgcaacgccg gcaatatcgt tcgggcgtcg atgttcgtcc gccagggcaa 22080 gcgcctaccc tgccgcgagt atgacgacat cctggtacgg gccggattcg acatgtcgga 22140 cgacgaaatg cggacgttct tggacgatga tggcgtgatc ctttgcgcct acaacaatac 22200 tcgccgccgt ttgaacgcca gggcgcgccg catcctcggc tacaagggtg tacaaccgga 22260 aatcggcgag aagctggtgt gcaccgggaa ccagcacgaa tatggcatca tgaacggcga 22320 gcaagcaatt ctgctggact tcaagccggt ccccgaaggc caagaagatg atgacgagcc 22380 ggatgaaatg ctgtttgcca aagttcgcat tatcggcacg aactatgagc gctgggtgaa 22440 gttcaatcct cttagctttt cggttgagga agatgtgcgg ctggaggcac agaaggccat 22500 tggcggattc gacttcggct gggcgatgac gttccacaag tcgcagggat cggaatggaa 22560 gcgggtcgca atgttggaag aaaacttgcc ttcaattcct tacagccagt tgatgtatac 22620 tggcataact cgcgcaattg aatacttgtt gtttttgcgt aagagttaaa aacttcgcta 22680 acataaataa gttccctgga gtctggactt tcccgaaaga aaaatattta gagaagttca 22740 ggcgaaaggt attcccttct tcaattagtt tagagataat cctctcacag gccaataagc 22800 catcctttca aacattcccg gagtaagaac atggaccaga acgaacagac ccaaggcgaa 22860 gagctgacca aggaacaagc agccgccctg cgcaaggccg agaaggccgc cgagcgtcaa 22920 cgtaaagagc gcgagcgcgc cgagaaggcc gaggccaagg ccaaggaagc cgaacagaag 22980 aaagccgagc gcgaagagaa gcgcaaggcc gagcgtgaga agaaggaagc agagcgcgcc 23040 gagaaggcga aggaaaaggc cgccgccaag gaggccgagc gtgctgaaaa ggccaaggcg 23100 aaggaagccg agcaggccga gaaggcgaag gccaaggaag ccgagcgcga gcagaagaag 23160 gccgagaagg aagccgagcg agccaaaaag gccgaagaga agaaggccgc ccaggaagct 23220 cagaaagtcg ctcgtgaaga agagcgcaag cgcctggccg agcagaagaa ggccgagcgc 23280 gaagccgaga agcagcgccg caaggaagag caggaagagc gccgtgcgaa ggccgaagcc 23340 cgtcgtgaag aactgaagtc caacggctcg cgtcgccctc gcgccaccca cttcatcccg 23400 accggcgacg gccatggcac cccgcaggcc atttcgattc gcggcaaggt gtttgcctac 23460 atcaacgaga actgcgccgt cggtgagccg gtagaaatcg aagcttttgg cgagaaagtg 23520 gcacacctgc tgtatggagc ctcggttcgc agctatctga gcaagctgga agtcatgggc 23580 tgggtcgatc tggttgccat cgcttcgaag gaagacgaag ctggccaggg cgatgacgag 23640 aaggccggtg atgaaggcca ggagcacgac ggtgaagatc agggcgccga cggttccgat 23700 ggtgaagaag agtaagccgc cgctcttctg agactgaatc gtctagctct tcaagggact 23760 catgaaaatg ggtccctttt tatcctctca agttttgtac actcagaagg aacacaccat 23820 gattcctgat cagaaagtca tcatcgtagg tgctggactc gccggactga tcgccgcgca 23880 tcgctttcct caagcccaaa tcatcgacgc ggcgacgccg gagaacaagg agcgtcacaa 23940 cgcactcttg cgattccgct cgccagtaat tggccaactc accggtatcc cgttccgcga 24000 agtcactgta cacaaagcta tctacatcga cggcgagttc atctcccagc cgcgcatcga 24060 ccactgcaac atgtactcca ggaaagtaac gggcggcctg tcggatcggt ccatctggaa 24120 tatggcgacc gaaaagcggt ggatcgctcc ggccgactac tatgagcagc tggtcgctaa 24180 gctggcgaat cgcatcagct ggggcaggcc tttcgacgcc tctttcttcc agttccttcg 24240 ccggcaagat gatcacgtta atatcatcag cacagcacca ttccgcgcca atctggctgc 24300 ggcaggactg gacctgggta tcgacccgtc attcggcgaa ggcacctcca tcgtcgtaag 24360 tcggtacaag ctttccattc cttgtgatgt cttccaaacg gtgtacttcc ccggtccaga 24420 agtcggaacg tttcgagcgt caatcaccgg tgatacccta atcgtcgaat ccattactaa 24480 gggagtggtg gagactgctg cgggcgaaat caaaaccatc gaatgggaca gcgcctggga 24540 cctggatgac gtctgctcgg ccttcggcat caggaagaag aatctcattc aggacggcga 24600 gccgaccatc cagaccaagg gtaaaatcat tccgctcggt cgcgatgagc gcgaatccat 24660 gatttggaat ctcacccatg aagccggcat cttctcgcta ggtcggttcg cgacttggcg 24720 aaacgtcctt ctggacgatc tggtttctga catggacgtc atcgagcgcc tgatgacttc 24780 ttcgtcttat cagaaggcca agcagatgtt cgtgaagtaa tttacaaaag tgctttactt 24840 ctggatcagg tgggcgtaat attccctcat cgaaacgcga aacccttcaa ccaaaaggaa 24900 tcgacaaatg gcccgcgaag taaccttctc caccgacaag aaccacacca aaacctacgc 24960 caccaaggcc aatctcgaac gcgctatcgc caaggccgaa tggctcggtg aaggcgcccg 25020 ctacttcata catatgaccg aggacggccg cctgactcct gtgttccttc tgaatagcct 25080 tcctgcaggg gccggtgcgg tttggtgcgc tcagcacggc tggaacgtgg taggttaatg 25140 gccgtcgatc ctcgcgaggc agcgctcaag cgggcgctgc tggctttctt cagggacacc 25200 gatgcccttg gcggcgggag tctcaccata acggcccgga tcgtcgggcc agagggtgac 25260 aggaagtttc gcgccagtta tttcctgaat ggcgagaagc tgagcctgtc agatataatc 25320 gctaaagtgg aggccgaaga tgggccggat cgttaatatc aaagcagtca tttctcgcac 25380 gaccgagcgc gattcgatgg ggtcgccgta catccatgag tcttaccgca ctttctcttt 25440 ctccgcttcc accacactgg tcgcggccat cgactgggtg aaaggccagt gcccggaaat 25500 cgttgacatg ctcatctacg agccggaaac cgtagctgct cagcaggagc gctattaatt 25560 tacgcaccag atcatcctga agaggttcct atgtccttcc tcgaactcga aatgcaagcc 25620 gaccagcagc cgaagaccgc gccgtctttc gttctggtag gcatcctgta tcaaaccggc 25680 gctgaactgg acgataagcc tttcacttcg ttcaacctgt cgttcggcag tcgagaagag 25740 gccgagcgcg cccgcgataa gattcgtgag cactacctcg atcgtcgaga tatccgcgcc 25800 gaaatcatcc gctgctactg aggtcatcat gtcgattgaa cttgtgtacc gaacctctga 25860 tggaaccgtt ttctcatccg ttcaggaggc tgaagagtat gagtcgcgtc tggaggcctg 25920 cgaactgctc aaggaagaga tagagcagta tggccttcgt aaagagcaag cccaaggcct 25980 ggccctggct ctaaccaaaa aattccactt cacgccaatt ccggaagatt tctgatgaaa 26040 atttctctga tcagttacac ccagaacgcc tgggaacttc tcctggggac gaaatccact 26100 cgcatgcgcg gccaagaccc ggcgaccatg accgaggccg aaaagcttga ccactggaag 26160 tacatgctgg acaccatccg ctcgccgttc gagttcgtgg acttcatttt ccagatcgag 26220 ggtgtcagca agaacttcac ccatcaactc gttcggactc gtaccggggc ttaccaacag 26280 gaaaccagtc gcgctctgga aatcagcgcc gtcgttcagc cggaagcctt ccgctgggaa 26340 ttcgacgaac cggttacggt aaatggcgag cctgacccga cctaccatgt ccgcgaagag 26400 ctgaaccgtc tgtggcatga cgccattgcc gacgcgcaaa ccagctacca gaagcttctg 26460 gaggccggcg cgtcgctcca ggacgctcgt gccatcatcc cttccaacat ggaaacgaag 26520 atcgcggcca agttcaatct gcggactctc agcgacatgg cgaaggttcg cctgtgcgtt 26580 cggacccagg gtgaatatca ggaagtattc cgcgaaatgc gccggctggt tctggaagtc 26640 tatcctatgt tcgacagcct gctccagccg cactgcgtcg ccaccggctc ctgcgccttc 26700 ccgcgctatg ggtcgaaggt gatgaatgaa gaggaaatcc agcagaaatc ctatgaccgg 26760 ttcatggccg ctctggagac aaagccaggt cagattcctg tgattgatgt tccgttggaa 26820 cctatctacc agtgcaagtt ctatcgcccc tggatggatc gctcggccga gcaggaagaa 26880 ctgcgccgcg atttctgggg atcggaaaaa caagaggcca accctgtggc cgtcaatggg 26940 aagtccatgt aacatgaaga tcattgtcga gaaagttgga gacatcgcac aagtcgaagt 27000 gaccaacggc agcgaatcca ttcgcatcac gatgaacgtg caatcgttcg atttcatcca 27060 gaatggcgaa gttttccgcc tcacttctga tgggacgttc atcgataaaa ccgtcaccca 27120 gaaagcaacc agtaaggaaa tctgaatatg gaacgcaaac caaagaatgg catcatcatc 27180 ttcgacctgg acggctgcgt attcgacgat agccaccgca agagcttcgc cttggaacgg 27240 caatgggacg agtatcattc tcgtctcgac aaggacactc tcaacccgca cgctgtaggt 27300 cgcatcagga atgccatcga cgccgacctc atgattttct tcgtcaccgg ccgaaccgac 27360 aaccactttt tccagaccag ggccaagctc caccgcgaac tcggcatcgc cgaacatcgc 27420 gagtatgaac tcatcatgcg gccgtatggt aacaccgagc cggcgcctca gttcaagcgg 27480 gcagtcgcgc tcgacatcct gaagaaaatc gaaggcgtca ccaagatcgt cgcggcgttc 27540 gatgatcgcc aggacatcat cgatgcctac aatagcctgg ggatcgactc ctacatcctg 27600 aacctggaag gttgcgctgc gccgttcttc gccgtcgcgg ccgatagcga ccccgatagc 27660 gcgcccaacg acatggcagg cgagccgttc ccggccgccc cgaactccgc ccctaccctc 27720 gacgaggcgt ttgcgaaagc cccgtctccg ctcgcggaaa cggctcagtc cgaagacccg 27780 accgaagacg ccgcgccgtt cgccatggaa tccgtctggc cgggcgaaga tgattcccat 27840 ccagatgatt tcgcggaaga tgttctcaac aatctgtacg ccgcagcaga agtcttccgc 27900 gcccgccaga gcacctatgg tcgcaatgat ctgatgtacg gaaagatcat ggaaatcctc 27960 ttcccgaacg gcctggtggc gaagaccgcc gatgatcatc gactcgccct gttcgtgatg 28020 cacatggtgg gtaaactcac tcgcctggcg aatagcgggt tcaaggatgc cgattcggcc 28080 ttggactcga tcaactattc ggcgtttgtt cacgccacca tgcgctccgg ccgcatcacg 28140 ccaaaagacg gacagaaggc gtaaatcttc agccgtcgcg gtatactcct caggccggtc 28200 gcgaaagcag ccggcctttc gacataagag ggaacaaaca tgatattcgc tgtatgggat 28260 actgagacca caggactccc gttccaccaa agggtgagtc tgagaaagca gccgagaatc 28320 atcgaattcg ccggcgtgat aactgatggc gaaaagattt tggatgaagt agagttcatc 28380 tgcaatcctg gaatcgtcat cgaggaaatc atcaccaaga tcaccgggtt gaagaacgaa 28440 gacctgatca agcacccatc tttcctcgat cagcgccaaa aagttcgcga cttctttgcc 28500 agagccgacg cgaatattgc ccacaacctg ccattcgata agttcatgct tacctgcgat 28560 ttggctcgcg gaaagctcgg cctggaagaa gtcaatttcc catcactcga tatctgtact 28620 gtggaagagt cggcgccgtt gttcggccac cgcatgcggt tgcaacatct ttatgagcac 28680 tactgcggcc catatgtaca gaaacaccgg gcgctcgacg acgtgcggct gctccacgaa 28740 gtctgcaagc gcatgggagt gtatcgggcg tatcaagcaa tggaggccgc ataatgtctt 28800 tccctcaact ccgcgttcgc tccggttact cctatggcgc cgcatatggc cgattcccgg 28860 agatcatcga gcgcgccaaa gagatcgaat ccccattcgt cgccatcgtc gatgatggaa 28920 catggggtca cgtccgttgg gagcaggccg ctgtcaaagc agaactgcct cgcggattcg 28980 gcatggaaat accgatcaaa tgcgccgacg acggcgaaaa agagctgaag ctcaaagcct 29040 gggtgctcgc caaggacacc aagaagttct accgcttgac ttccaagtcg gtccagaatc 29100 aagggttgac tccgcaagaa ttccaggaag ctgacggtgt catcaaattc gctggcgagg 29160 cgtatgccca tttggatctg gccggaatcg actacattga catcaatccc gcgtcgatgg 29220 tcgccgcgca cggcgctatg gagacggcca gggcattcgg aaagccggtg gtaattacct 29280 cttacaacga catgccgtcc atcgaccatg ctgatttcgc gtcggcctgg aaggtgcggg 29340 aatcggtcgg ccttcgccac atcgccaccg aagaggagct gtggagccgt ttacgccaca 29400 tcatgactcg cgaagagttc gattccgcca tcgccaatac tcgtgcggta gtcgagcagt 29460 tggcggatgt gaaactggcg aaggcgccga tgatccatct ggatggtgat atcgtcgctc 29520 tggctcgcga ggggcaagcc taccgcctca gtcgcggcca catcaaggaa tggacccagg 29580 agtatgagga tcgattccaa gaagagatca agcagattca gctgaaagat ttcgacagct 29640 acttcctggt cgtggcagat ttggtcgcgt ttgccaagaa gcacatgctg gtcggtccag 29700 ctcgcggctc ttctgccggc tctttggtct gctatctcct tggaatcaca gaggttgacc 29760 cgctcccgca tcgcctcctc ttccagcgct ttatcgacat ttcccgttcc gatcttcccg 29820 atatagatat cgacttcgcc gatacccatc gctatctagt gttcgaatac ctccagcaga 29880 agtatggcac ttggaacgtg gtgaagttgg gtaacattaa cacgctcaag gccgcatcgg 29940 ttatcgctca cgtcggaaag cgcttcggca tccccttcca cgataccgac aacatcaaaa 30000 actcgatcat tgaatatacg tcggcggacg aacgatatgg aaaaggattg gaggacactt 30060 tcgaaaaaac tcaacccggc cgcgacttcc gcgaaaagta tgagatcgcg tccgcctgca 30120 tgggcgacct cgaaattcac ccatcccact ctggcgtcca cgcggcaggc atcctggtct 30180 gcaacgatga agtcatcaac ttctgtacgg taacttctga aggcgtcgcg cagctcgaca 30240 agcccgattc ggaatatctg aatcttctca aaattgatgc gctcggcctt cgaactctgg 30300 gagtcatcca ggacgcgaac tgcgtgaccg cgcaagagtt gtacgacttg cctttgaacg 30360 acaaggcggt tctggacgtc ctcaatgaag acaaaatgtc cggcatcttc cagttcgaag 30420 ggcaggccgt tcgctcggta gcgaacgcga tcaacatcac cgcgttcgag aacatcgacc 30480 acatcacggc gctcgcccgt ccgggtccgt tgtcttctgg tatggcaacc aagtacatcg 30540 agcgcgtggc cggccgcgag cctgtgacct ataccattcc gcaggtcgag caatatctgt 30600 cagggacgta cggcgtcttc ctatatcagg aacagatcat gtccatcgtc aaggacatcg 30660 gacagttcga ctgggagcag acatcggcaa tccggaaagc catgtctgcg cgaaagggtg 30720 aagagttctt caacaagcgc cgggaattgt tcatcgaggg tgccaagacc ataggcgtcg 30780 ccccggacga tgctcaccgt gtgtggcagg aaatggtgac attcggcgcc tggggattca 30840 accgctccca ctcggtcagc tacgccgtgg tgacgtactg gacctgctac atgaagcggt 30900 atcatcgcct ggaatacgcg gccgcgtgtc ttcgggcggc gaaagacgac cagcaaactg 30960 tgtcaatcct tcgcgaattg gccaaggaag gcgtagaata tacggccctg gacccggagc 31020 attccgaact taactgggta gtggcggacg ggcgcctgat cggcggcatc atgaacgcca 31080 aaggcttcgg cccggcgaaa gccgagaggt tcctgcgcct tcgcgaggaa gttaaggccg 31140 caaggatcgc cctggccaat tgcccgatat cggcacagga tgttgaggac aaggctgctg 31200 atgtagcagc gctggaagcc cagattcttt cggcgaaaat cagccaagac aaagaactgg 31260 aaaaactgtt gaaggccgat ctgaaggagt taaaggcaga tcttagggag ctgaaagctc 31320 aatataaaga gctggccgga acccacctga agacgcttca ggattgggag aaagtcgccg 31380 cgagtctgtc gaattctgaa gttcaattcg cagatttgaa cgaagctcac acgctctggg 31440 gtcatgctta tgacaatccg gagctggttg gagtaacttc cggaaacccc atccagaaca 31500 ttcgggatat ccgcgatgga gacgatggcc tggtcattgt caagatggtg aaaaaagttc 31560 tgtctgatga gaacgaaccg attcgccaga agaagagggc agatcaaggg aaaaacccgg 31620 tgtacaaggg ccagtcgcag tttctcgaca tcatgtgtgt tgacgactcg gtcgatcagc 31680 cgatacgttt cagaattagg cctgaaaaat atctgcaata cggaaagcag attgccgaag 31740 ggacgccgac cggctcttgg ttcctgatca aaggctggaa gctcagcgga atcgatatgt 31800 tcatcgtgaa ggccgtcaag aggattttga ccgaacgcga aaaagcaaag ctggcagcgc 31860 aagcagagaa agtttccaaa gagggcgaag gcgatgaatg atcgcgaaac gaaagcggcg 31920 aatacgttta agcaacgctc gctcggccga atcctgatcg actttctgga gacgcggcgg 31980 tctggtatgt ccgattcgat ttgcctgaat cgtcgaggtg tccagttctg ggtcgagttc 32040 aaggcgttgg aggagtggcc gaaacgcgcc tccacctgcc caatggccag atgtttcgag 32100 cctgggcaaa tccctttcct tcgggaacgg atcggctggg gcggccgggg cttcgtcctg 32160 gccaagatcg ggaccgattg gctgctgctg aatcccatgc tcgatttgtt cgagcttaac 32220 agccgcgact tggtggaagt tgcgagctat gcagaaggac tggataacat tgttcagttc 32280 ctcgccgatt tggagaacaa atgaaagcca aaacatatcc cgtcaagggc atgaagaccg 32340 aggccatgca gcaccagttc aatgccctgg ccgcgtccct gaacaaacgg aatttcgcat 32400 acctgatgga gcagggcacc gggaagactt ggacgacttt ggccgatgcc gttcgcctct 32460 tcctacaggg gcgcgtggac gcgctgctca tcgtcgcccc caaaggcgtc cacaccaact 32520 ggattctgcg cgagattccc acccacgtcg cgatcaagac tttgagcgtg gattggcgcg 32580 gccgaccgac ttccaaaaag gccagggcgc gcttggatcg tctgtatgcc gagacgttcg 32640 cagatgaaaa agttcttcgc gtcttcgcca tcaacgttga cgccatcaat caccaggctg 32700 gctatgatga agtcttgcga ttccttgaaa ctttcaaggt ttgcgcaatt gttgacgagt 32760 ccacgaggat caaaaacccg caagccaagc gtgcgaaaaa gatcgtaaag ctgggtgaga 32820 aggccgtggc ccgtcgcatc ctttccggaa ctcctctaac gcgggcgcct accgatttgt 32880 tcatgcagtt ccaattcttg cgcgatggaa ttcttggaac gaaatcctat cgggcgttcg 32940 tggccgaatt ttccgttttg gttcccagtg acgatcctcg aatgatcgct atcatgcgca 33000 agctggaagg gaagcaaacc atgccgccgc aactggtcga aaaagacgag cgtgggcgcc 33060 cggtattccg gaacctggac aagctgcggt ccctgatcga gccgcacagt ttccgggtca 33120 cgaagaagga agcactccca ttcctgccgg acaaggtgta caagcgcata tacttcgaaa 33180 tgtcgccgga gcaacgaaaa gtttaccagc gcgtggaaga agactaccac ttcgttctca 33240 agaacgaaga cttcatgctg gacgtatctt tcgatgctgc ggcagcgcgt tcgaagctca 33300 agcaagttgc atccggctat atcaacgtct atggcgagcc ggtgatcctg ccgcccgaag 33360 acaacccgcg attcgccgtg tttactgatc ttctggaggg tctgctggag gaagacccgg 33420 agcgctccat catcatctgg gccatgcgca ttcaggaaat cgaccagatc aaggcgtatc 33480 tggaggccca aggaatttcg tttggcacat actacggcga gaccaaagag gccgagcggg 33540 aaaaattgat cgacgatttc caggccaagc gcgtccaggt gttcctgggc aacccggccg 33600 cagcagggat cgggatcacg ctcaccgccg cagacgtggc catttactac acgaccgacg 33660 aagacaacga gctgcggatg cagtccgaag accgaaatca ccgaatcggc accgtcaact 33720 cggttttgta cttcgacctg atctgtctgg attccatcga cgagaaaatc caggtcagct 33780 tggagtggaa gcgcaacctg gcaagttatg tcgttgatgg agtgtttgag gctgacgtta 33840 gcactcgcga cgaaatttaa tatgtaaatc agtagccgta tcaaggaaga tgcggcataa 33900 tatctactca atacttagtt caagtaaggg aacatcacta agttggaggc ggacatgaaa 33960 gagcaagagc ttgaaatccc ggaatacctg aaagagaacg caccgggcga aatcgactat 34020 tttggcgtca tggatgaaat ggcggtcgaa gccaccgaca tcggccatcg actgctgaac 34080 ctggtggaca aggcttcgca gctggacgtc gaaatcctcg atcttcaaaa ggcgctggcc 34140 gaaaaggaag aggagctgaa aaccctcaag cgcaacacca ttccggagct gttggaggag 34200 cttggtcaaa agaccactac tctggcggac ggtcgcacgg tcaaagtcga gccgaaggcc 34260 atcatttccg tcaaggaaga gaacaaatcg aagttctgga agtggctgga agacaccgac 34320 aacgacggca tcatcaagac caaggttctg gccgagttcg gtcgcggcga aatggaagat 34380 gcgaagaagg cggccgaggc catcatcgaa gccggctatg acgccaccat caaccgcgat 34440 gtccattacc agaccctcca ggcgttcggc cgcgagtatc tggagaaggg cgaagagctg 34500 ccagatttca tcggcgtgca cgaatacaaa gaggccaaga tcacgaaacc gaaggtgaaa 34560 aagagcaaat cttaatatgt aatttgcttt acttagttgc aacttccgtt attataaacc 34620 cacagttagc gataactgaa attcgacaaa caaggagcct aacatggctg gtaagaaaac 34680 cgaaacttcc gaagcaactg aagaaaccaa ggccgttgca gtggccaacg gcggcgccgt 34740 cgcgactact gacgttcccg acttcatgga cctgtacgcg tatgacggcg ccggtttcga 34800 aggggctgac gcagattcct atgccattcc cttcatccaa gtgctgcaaa agatgtcgcc 34860 gcaggtcgat gaagacgatc cgaagtacat cgagggcgcg aaggccggca tgttcctgaa 34920 taccgtcacc ggcaagattt acgacggcaa gaccggtctg ctgatcatcc cggccgcgta 34980 tcgtcgcgag ttcatccgct gggctggtcg cgaggccgag ggcggtttca aagggtccat 35040 cagcgtcgaa gacttcaagg aaatgatgaa agaccctacc aaggtcaagg aagtcgaagg 35100 acgcctgtac gcgccgaacg aagacggctc ggtcagcgac aagaagtctg actacttcgc 35160 cgacacccgt ggtcattacg tcatcgtcat cgatccggac accggcgatt tcggccaggc 35220 tctgatctcc ctgtcgtctt cgcagatcaa ggcctcgaaa aagctcatga ccgcgctgtc 35280 ccagaaaaag gttcagaccc cgcagggcct gcgcaccccg ccgactttcg ccaacctggt 35340 ccgcatgacc accgtaggca tgtcgaacga caagggcagc tggtccggcg tccagttcga 35400 gctggaaggc ctggtgaaga acccggatca cttcaaggct gcggccgacc tgtacaagtc 35460 gttcgtcggc ggcgaggtga aggtggacta cagcaagcag gaacagcctc gcagtgacgc 35520 cggtggcgtc ggcgatgcga ccgaagccga agagttctaa aaatcaccgg ccggagaaag 35580 gcgctgtaat ggcgcctttc ttctgaggag tcgaaaatgg actggaagga cataggtagt 35640 aagatcggcg cggctgcccc ggctcttggg tcgctcctgg gtgggcctgc aggcgccgcc 35700 gtgggcgcta tcgtcgcgac ggcgctgggg tcgaaggccg acccagcctc ggtcgcgagc 35760 gctctagacg cgaatccgga agctctagcg cgcctcgccg aactccagag cgccgagcgc 35820 gttcgtctcc aggagcttgc gattcaagcc gaacaaaacc gccttcagtc tgagcagaac 35880 cagctccaag ccgagcttag ccagttcgcc gcagaggctg ccgacaggga ttcggcgagg 35940 aggcttgccg cgcagcagaa cgatttcgtt cgcccgtcga ttacattcgc tcttctgaca 36000 ggctccatcc tcatcatcat cgcaatcttc accttcggcc gcgaggctct gatggacccg 36060 acatcctcgg tcgccatcgg caccatcatc ggctattggt tcgccgaact gaagtcggta 36120 atggcattct acttcggcac caccaaggat ggatcgcgcc agagcacggc gtccatcatc 36180 aacgcagtaa aatcccaaat acagaaggaa tcgaaagaat gaacatcgaa caaatcatga 36240 gtcgcgaact tcacgacctg gttgtcaaat ggggcgccga ccggaacctg atcaaaggct 36300 cttcggccaa agatcaattc ctgaagttgg tcgaagagtt cgcggaagtt tgcgaagcct 36360 gggtccagaa caacccggtc gaggtgaaag acggcatcgg cgacgtaatg gtggttgcca 36420 cgatcatggc cgcgcaactc ggcgaaaatc tgttcgatca tctgtcggcc ttcatcgaga 36480 ctggcgaagc ccatcccacc tacggcgacg atttgcagcg cctcggacat cttgccggcg 36540 cgctggcacg cggaaatcag ggatttgcca tcaagagcct ggtttcggcc gtcatgactc 36600 tgttcgacgt gacggaagag cacgacacca ccatgctcga ctgctacgct gcggcctacg 36660 acaccatcaa ggatcgcaaa ggcgtcatgt acgacggcgt gttcatcaag gagtcggacg 36720 agcgctatgc gtcgatcatg gccgaactga accacgccaa cgaaaccatc tgagccggct 36780 taccgccatt tagcccggtt cgccgggctt cttttctgga gaactgtatg aaacccatgc 36840 tcgcatcgaa ttttgacccg aagctgctgg aaggccaact gccgatgtat ttctcgccga 36900 agatcgatgg atttcgctgc ttcgtattcg aaggcgaggc gctgactcgt caactcaagc 36960 ggcagaacaa tcaatcgatc tacgaatacc tcagcgataa actgttcaac ggcctggacg 37020 gcgagctggt ctgcggcgac atcagcgacc cgaaagtttt ccagaagtcg tccggcgatc 37080 ttcgccgcca cagcggtgag ccggactggt ctttccatgt gttcgatgat ttcaccgatc 37140 ctcgcgcacc gaccgaagat cgcctagcca gggcggccga gcgcgtgaac ttccttcgtc 37200 actgcctcgg ctatgagagg attcacctgg tcgagcagga actggtgact tccatcgaac 37260 agttcagcga agtcgagcgc cgccacacaa tgctgggatt cgaaggttcc atgggcaagc 37320 gcgctgatgg gctgtacaag ttcggtcgct cgactgccaa ggaagggcac tgtgtgaaag 37380 tcaagcgata cgactacgat gaagctgaga tcatcgacgt ggaagagttg atgcacaaca 37440 acaatgaagc tttcatcaat gaacttggcc acacggcccg ctccagccac gcagaaaacc 37500 tgtcgccgtc cggaatggtc ggtgcgttag tctgccgcaa cgaacgtctg tggcctggag 37560 tcaccttcaa cgtgtcggcc tccagcctga cccacgacga gaaacagcgc cgctggaatg 37620 acagggaata cctcaagggc caggtcatcc gattcaagca cttctcccat ggcgccaagg 37680 acaagccgag acacgccgtc ttcgattgct ggctggacgg atggggcgga agccactgat 37740 tctagaggac actagatcga aataaacccg gacgccttac cctacaggcg atccgggttt 37800 tctcgtttta atgtcgacaa attaggcctt agaccggacc cggccgccag agttccttgg 37860 ccagaaagaa ggcgatttaa tatcgcggtg cgtatcgtta aacagttaag cgcgagcatt 37920 ttcgacgagt tataatagcg cccgaacctt ccgattaaca cagcgcatcc ccaagccatt 37980 atcggggtga ggagaagacc gcagacagag gactaaacat gaaacgcaaa gagcatcgca 38040 agcgctttcg gccaagaatc agccccagac tccgggaaga gttaatatcc gttctgacca 38100 agatcatagg cgagacagtc aaggacaagg tggtaagagc gctgttaatc ggcgttctga 38160 gttcactagg gaactatgtg gattcggtca ctcaggaaga gtccgccgcg ccggttgaag 38220 tcaagatggt tgaagaggca aagccggaaa gcaaaaaggc cgctgaataa gcggcctttt 38280 cttttgggcg aatatcagga gccttgattg atcgcggcga tggtcttcat atagcggttg 38340 atccggagct ggccatggtt cgcatcgttc ggcgcggcgc cgttgatggt tttcacgacc 38400 atggagaagt tgttggattc cgccatgggg atgcagcgat tgcgccagaa gaaccaggcc 38460 gaagacatcg acgcgccggc cggagtttcc agaagctccg gcttctccag aacgtccatg 38520 ccggagtctt cggcgaacag agaatagttc gacttcccgg tcagctggat taagccgcgc 38580 ccgcgatact tccaaccatc gccatcctgc tcgcatccat tacccatgcg atccgcgtac 38640 acgttgttgg cgatggcaac cgggtttcgg gccagacgat tcgccagagc attcgggaca 38700 tacgggcgga ctcgcgggtc tactgcgtac cggcgcggcc atgtgttggc caatccttgg 38760 gcgctgtagt tgagattctc caccagactc accagtccac cggactcgac gccgatgttg 38820 gctaggtagg ccgcaatggc tcgcggcgac tcgatgtgga acttgtccat ggccgcctgg 38880 acatcatcca gccacttgat cgcccgatcc gtggtgcacc cggttccggt gataagaata 38940 tcctttgtga ttttcatcaa tactcctgat ttttgaacat cgttttcaga gccatgggaa 39000 gtcgcggccg atccccgcta ttccaatcgc gaatctgctg cctccagtga acaagggctg 39060 ctatcaaccc aggtccgtcc gtggtttcga tacccagccg cctctgctcg tcgtgacgat 39120 ctatgggcca gcgggtatca cgaaggatag cccgcttttc cctggcccgt atagcgtcct 39180 gcaaggcctg ctcccgcttc gcatcgaccg gggcgatagg tccgtgcgcc ccggatagga 39240 tcgcagcgtg gatggccctt ccgtgggcct ccacgtcgtg cggattggcg gtgaaaggaa 39300 cttccccgat cccatcgaaa gtcaccatgg cgtggatgtt tgttttatcc agccaacgag 39360 ggtttctgat ccgcgtccat ttcattttac gtcactcgct ggaaaagggt cgcggagtca 39420 ggagtgttgg catcccggtt gactacatat cccatgcagc gccaagttcc ggcaggcctt 39480 tgaccgctat tgtagtttgc ggcgcaagac gagtagatga gaatggaacc gtccacaacc 39540 actcccggtt gaacggtcgc ggttggagcg gcattgtcca gaaccgcaaa gatgccatag 39600 gaaccgactc cgccaagacc cacctgaacc agcgcctggt tgatgtagtt attgtagttc 39660 ccggcgtgga tgaccggata ggcgtttgcc cccaggtttc cgccacctac tttgagaacg 39720 ttgtcggtat ccaagccgaa gttgacgaag atactgccgc cccgctcgaa agtgactgcg 39780 gccgcttgcc ccgaatgcgc cccattctgc aggttgatgg cgccaactcg accggacgaa 39840 gctatgccgc taccagttcc agaaatgcgg ttgaagacca tgttgccgtt ggtggcgttc 39900 gcggcgttca aatccacttt cgtcgccgga tcaaagtttc cggatcgcca aacggtttgg 39960 ccgttccagg acggcgcggt cgggttggcc gcccaaagat tcatgatgtt gctggaatcg 40020 gcgatttccc tggaactgtt gccgagcgat ccgccgcccc atttcagctt gttgtcggta 40080 tcgatgccga agaacgcgcc ccagttgcca ggacgaatga acgcgatgac ggccggtttt 40140 gcagacggac cggttggcga gttgtaaacc gtcaaagggg cctgagaata atcggacagc 40200 gatgcgattg gagcgaatgg catagttccg ctgaatatcg cagtgctgct agtttcctgg 40260 gtgccggctt tgatggtcag cttggtgttc ggattaaagt tccacggccc ccagaattcg 40320 tttccgcccc aaacaggagt gccagccatg gaattcacgt ggaaacgaat gttggattcg 40380 tcggtaatca cgtaggcgtt attgccgagc gaccagcctg ctcgcttcag ctggccgtcc 40440 ttgtccatgc ccaaatacca gccggtttgg gagttgtcga agtagatggt cgcaggctcg 40500 ccaccccctc taccgaagat ttgaatggct gcgtttccat acgatgcagt tgtggagctg 40560 gagccccatg tgttcatatt tccggtattg ctggtggtat tgcgaattcc ggtcggtccc 40620 gaaatgttgt tggtagtccc gacagtgagc ttggtggccg gatcaaagtt tccggagtcc 40680 caagggacat attgtccagc aaacagaggg cgattgttga atatgacgtt cgtggacgcc 40740 cagtcccatc gcatgatctg tgagcgatag gagccgtccg gattggtggt attgactgcg 40800 ataaccgcgt tgttgttggc gtccacacct tgtgcgaagg tgaatttcca accaggctga 40860 tcggcagtgg tgttctgcca aaggggacca gagttcgcga tgtacgcgag gtttttcgca 40920 acatccagtc gcggctggag gaatgtaaca ttcgacctgc tgaacaggat atcctgggta 40980 ggaccagcgg acccctggcg agagtagaac gccatcgacc catcagcttc agagataaag 41040 cgatagtcga agtctttggc gcggttgttg ttgaagtgga aatcgatgaa aggccgagcg 41100 tcagacaact ccagattggc gaaccacggc gtagtgtctt ggatagcgac gttcggcttg 41160 ttgacgacgt cagcccagtc cacttcagtc agcttttggg acgcgacgta atccttcacc 41220 tgtttccagc tgggggcctg gtaatcttga tcggcgttgc caacttggat gcgtggcgcg 41280 cctgcgagga ttctccagcg gtcgcctgct gcgtcgaata caagctcagc gatgagtcct 41340 tggccaagtt cgccgccggt gagagggaag ttggccgcgc cgacgatggc tttggcgccg 41400 agtccggaga cgttgatggt ggaggcgccg gtgttcatgg tgttgaactt gacccgaaga 41460 atcatgccat ccaccaggcc gccttggagc tgcggaacta gcgtcaacgt gtaagcgttc 41520 gccgatccgg ccgcgactcc ataggtgacc cgaccttgtt gaagggccat gacgtttacc 41580 gcatacatcc agttggtcca cgctccggca ttaagcccgc gcacagcgac gttcccgacg 41640 cgatcagtgt agcgttggac gcagaacgta ttggctccgg acacccaaga tttcgcctcc 41700 aacatgccag cagcggcacc agcggaagcc ggatatatgg gggcattctg agaagcgata 41760 accactgaat cagagaagaa ctcccacgtc ccatttaaca ggtcgttgaa gttgcggccg 41820 gtcgtgatga cttctccgcc agaagatagg cctgggcctc cggccggcat cgggatgttg 41880 gagcgcatcg ccgaccatgc gggttgttct tcccaagtcg tgctgctgag agggtcgctc 41940 gcattggcat tcaccatgga acgataacgc cgcattatgc cgtcatttcc gacgcgcacg 42000 acttctgcat tctgttcgta gccgccaggc atgccctgaa accacggcgg cgccatttgt 42060 cgctgccacg cctgtgcgtt ctgggtcgcg atgaagaaga gttggttttg aattttccgc 42120 tcgaccgctt tggcctgcgg gttgttcgac gccagactga tttcatagtc cggcgtatag 42180 ccgtcgcgaa ggtttgcgaa gccagtggag gaggtttgtg gaatcgggtc tttatcgccc 42240 tgagcggcaa acggactggg gatcagttcg ggtgtgatca cgtcattact cctgaatgac 42300 tttgacatcg caaccggcgc aagtcggcat aataccaact gcccggtcat tcatgaggtt 42360 gatcaattgc ggcgacagat taagcgccgg accaaccctg tattctagct tgaacgcccc 42420 actggtgggt aggccgatgt atgcggggtc tgacagagta aacgtatcct gagtcccatt 42480 cccgactgcg aatctggccg gttctgctgc agtcccgcct ttccagtctc cagtccaata 42540 cgcttctact ccggtcggaa ggggctgtgt gaacttgact gttccggtct gggcgttctg 42600 caaaacataa tcggtgatgg ttacgggcgc cccggtagtc ttcaagtatc cagttggagt 42660 atcacccagt tcgatctgag cgccccagat gagcacgtca atcgccgcgc tggaattcga 42720 atcaatccag ctgaagttgg tttctgccgg agcgacgtaa gcagcgcgga acgaagagct 42780 gacggtcttg gtcgtgagaa cgcaacgcca ccagccattt tccagacgaa tcattcgggc 42840 gcttaccacg ctgctgtcca gcatctgatc gctgattacg ttcccggaat ccaggtcgaa 42900 aacggcatcg gctcgactgg ggaaatcggc agccgactga attgcaatga aacgggtgga 42960 gccggctttc gcgaagaacg agaacgttac agtgctaccg gaccccagcg gcccatctat 43020 cggcgcggag acgtaagcgg tactcccggc cggcttagta agcttgcaca ccgtagcgga 43080 gccgtccggg gccgtagcgg acgccgtttc gaccgttacc ggaattccgc tcgcggccgg 43140 atcgactcct ggccaatcgg cgtcgctggc aggggtcgat gtcagcacgt ggttcgttct 43200 gggcgaactg gacaacaaca ccataccttc ccaatctttc cgatatactg ccaagttctc 43260 cacagggcca ttctcgccgg ttgagtccat gagatagaag tacagaccgg tcgcctcgtc 43320 ccatggctca tcatcattga atatgtaacg aagcatgcga ttgatatatg caatcgagcc 43380 gttcgaaatc agcgctacat atcttagctg aagcactttc ctgatttcgt ccaagttgag 43440 aatttcggca ttgccgccac cgtagaagtt gccgccaggc gatgcgtctg ccggtggcgg 43500 aacttgtgta ccgctataga tgaagttctg gcgtagccga ccgaatgccc aagaactgtt 43560 ttttggataa aggccgaacc ctttcgaagg cgtgccgagg atgatgcacc aaaccataag 43620 gccgaacggg ttggcagttt tcaagtggaa aacgtcgcgc tcccagttgg cccagaattg 43680 gcggctgaat ctgtcatacc attgcgcctt tctctggatc aggccggtga ttccaggcgc 43740 ctggttatgg agccatttca gagcttgttg gatgtccgaa ttgtacgcag gcagagtcat 43800 acgaaagtca cccgaacgtt accaacggaa atggtagcct ggccgaatgc gctcatgacg 43860 tattccgaag tgaaatcgcc cggagccgga gccggcgagc cagccgcgac gcacgcgacc 43920 tggcagagtt tgatgtagat gccgggaatt tcgcgagcga tggcgccggc gacttcgaat 43980 gccgacaggc tcgcgcccac caccagcccc tcttcccctt ccactttccc ctgggcgtaa 44040 ttgaccactg cgttctgaat ggcttccgga gctacagagg aggaaccttg ctggactgtt 44100 acgttaacat atccatcgta catgattggg gtggtccact tcacgacata ctttcgaccg 44160 gacgccggat cgcgcacagg aacgccattc ggaccgtcca ccgggacgcc gttgttcgcc 44220 gcgccatagt cccatggagt tccgccgtta tgggcggccc acaacgcatc ggcgactgct 44280 tgtttatccg ggtttccggc gacgcagacc caaacagcat acggaagggt aaacgagact 44340 ccattcacca cttgaacggc gccggtgttg ttctcgatta cgttcaccga cgtgacgttt 44400 ggaacggcgc tcacatacgc cttgatggcc atagtcgagt tgcggccttg gatggccaat 44460 cgattaacgc gggcattctt caactctgca tcgctcattt ggcggctgcc cggatcgacg 44520 cgagtggagg cgatgacttt cgctccggac catccaattg ttccgtcgat gatgatgaga 44580 ttcccgaccg gcagaggaat gttgccatac tcctgcgatt tgatatcgat ggtcgcgaca 44640 ccaccagcag ggatcgtgac atcgctcatc actgtgaaga tcgcgccggc cggagtctgg 44700 accctagacc cggtggaaat gcgggtttgg ctgcggccgg tgacttgaac tccatagccg 44760 aaggttgaca gatcagaacc gcgctcgatc cccatcaagg cacagatcgc gtccaggaac 44820 gttccgaatg aaacgttcgg gtttatggta ttggcaattc gcgcttcatt ccgcatgaca 44880 ctggaacggg cgatggcctc ggccgcgaca agcgatccct gcggagtgct cgcggccaag 44940 ttgatattgg caccgagggc ggcgcggaac tcggcctcaa cgtcactcag aacgtcggcg 45000 gtatctgcga ctatcacacc agtatcgacg atgtagttgt agttagccat tacaaccccc 45060 ccccgctgtt aaatcagaaa aatcaaaact tgccatgaaa atctccttaa gcaatcatgc 45120 cgcctttcgt ccgggcatca ggcgggttgt tttcgaggtg gccgtggttg ttcacgttga 45180 cgccgtttac aaccagggtg ttggcgatag tcacacttcc agtgaaattc gcctgcggag 45240 tatccacggt gacattcgac ggcgcagtga tcttgatgtt gtcgccgcga atcgaaattc 45300 tggtcgctcc ggaagtcgat tgtatgacca tagcggccga atcttcggaa ttgatggtgt 45360 atcgacggaa tacgtccggg atgaacaggc catgctcgaa cttatggatg cggccggtgt 45420 tcggcttcga cattgacaac gactccagga actgagacgt gtcgcggtcg gccgcataaa 45480 tccagcctat gtcaccttgc tgaatcggga agcttatgtg gaagccgcca gcccccatgg 45540 aaattacagg aatatcaacc agctgatgcc tttggacggc gttgtgttcc gtgtcaaccc 45600 aggtgatgag aggttgaatc gtcgcgatat tctcggccct gtcatattga acaacctgag 45660 ccggtatcat tacttcgaaa tctagagcat cccgccgcga ccgagcgtca agagcggcga 45720 tcagtcgcgt cctgtcggga gcttttgcgg atgttagaga aatattggac atgggaaagc 45780 ctctgatttg gcaggtctag tatagccttc ccaggcccgg ttaggaatta tccctttttg 45840 attctgttgt gcgatgcttc ggacgccaag gcctcgttca cgctcttcgc cgtcatgatg 45900 tctatcatct tgaacgcatc ttgagtcgaa taatactctt ccaactcgcg catagaggct 45960 gagccgttcg cgaccaagct cgcaactaca gaaggtgaat gtgccgtctt cacgcttttg 46020 atatcttcga caaatctgga tggaatcttg actccggtcc agtctttgag aaaaccaaag 46080 ttccagtcga ttaccacttc ggacagaagt gcaagaactt gtacgggagc tattactttc 46140 gctcgatcaa cgacataaag attgatgttc gcagcagtca atggaagcca gatgccttcc 46200 ggatggtctt ccggatgcgc caatacatcg gtgcacttga gcaattcttc tggcggcaca 46260 ctctgaattt ccgacatcat gctgagccca tcgacagcag agaattgccg cgaagtatag 46320 tggactccga acatgttgaa tgatttgatt tctctggcca ttatgccgct ggactcccca 46380 tgactttgat atagaacggc cgatcacgac tggccaaatc gtattccaga gcagtaatca 46440 catagttacc attgacgctt gggttcatga gcgattcgac cgccacgcct ccagccacgc 46500 gaatcgatgg ctcaaacaga cactggaatt ccacgcccca ttcagaccaa gatggaatac 46560 caacaaacga gttgacgttg gtcacctcat ccggacgaat gactttatct cggtccttca 46620 cgatcaatat gtcatcatcg acgaacgcgg ccacgtccgg catgtacatg tcctgaatcg 46680 acgccaggat tgccgacgcg acagtgatag accggcccgg attcttcaga acttgatcgt 46740 tgtaactggt atcgcagatg aagttcaatc ccatttcgtt cgcgccccac tcgacgaact 46800 tgacaaacgt cgtgttggcg ggcggcatat tccgaatggt cttcgtcctg tcgatttgcc 46860 tggtatagca ctggatgcgg attccaatgt ccggtggcgg agaaatgata tcgacaatgg 46920 caacttcgcc gacaaagact ctggaaactt gctcgcgccc ctggtcagag tagccggctt 46980 ccaccgacac cttgatcatc aattcatctt ccatgcccac ttgacgttgc cgatgcttcc 47040 acgcggtgaa ctgcgacaga agagactcgc gaagctgagt ggtgaggccg aaaatttcca 47100 tcgtcgcccg gttctgaatc cgcaacgcag ccttcataat ccggacccga acatccagat 47160 cttcgcggat gacttcgggt ccataaggca tgttgaatgt tactcgcaga attctctttt 47220 tcatcagtag agtatcttag ttgcggaatc gttttgagcg tcctggattg ccgtagtcag 47280 ctggtctgca gtctgcttac tgaatatctc gcgagcctct tccggagaat tcgcgccggt 47340 gacgttgacc aacatgtcga ttcgaccgat ggtcagctcc tggccgcgct ctggagcgct 47400 cttcagaagt tgctcgccgt acgtccggag aatatccatt tctcgcgatg cggcgttcac 47460 cttggccgtg gcttcggcaa gcttggctgg agacaggaat acgttgttgg cttcggtcgc 47520 ggcggccttg atctcctgtt gcttgcccag gatggcttgg ttgtatccga acagcaagtc 47580 agaacggctg atttcgcggc gcatgatctg gtttgggtta acgccgatca cttgcgcgat 47640 ggctccggca gtgagttgag cctggatgtt ctgcttggtc tcgccgcgaa cttgattcgg 47700 gaacttccgg aatccagaat ctgcccggtc ggcctcttga cgtctagaca tcttgaggat 47760 ttcaccgtcg ctgcggtctg gcatgcggtc gatgatgcga atctccggtc gcacaaccct 47820 gtcgtcatat cgacgggctt cgcggcgctc atcttccttc ttgccctggt ctggggtttc 47880 cagtcgcccg ccatcatagg gacgaatgtc catgtcgccg ccttccgggg cgaacgtctc 47940 gttggcgacg gtcatggccg cagccttctg cttgcgctga gcctcttcca tcagctcgat 48000 tggagcgctc attaccaaac ccggatatgc gcgagtcctt ggaccccagt tcttcggatc 48060 gagtccgcca tgatagtagg tcaaggccaa ccgcatgtcg ccatttgctc gatctaggtt 48120 ttcccgcagt aggcgcgttc cgccgaggat gttctggcga gggtcatata cgtcagtgat 48180 accatacgcc ttggcgattt ccggcatcag ttgcatgagg cctttcgctc cggcttcgct 48240 ggtggccctg gcgttgaatc ggctttcggt gtatatgagt ttcttgatgt ccagctcagg 48300 aatgttgtac atcttcgaag catctttgat gatatcgttg atgtacgatg gaacggtgac 48360 cggctctgcc ttgcgctgcg gcgagaacat gcgattgcga agagactggg cgccgattgg 48420 ctcgccgaag acttgtccgg ccgcgccact cttcgactga tcatagatcg cgtgcggata 48480 gacgccggtg gcccgcgaag tcggcgcggt gcttcccatg ccgaccgccc gaccaatttc 48540 ccccgcccag gctgcccaag cttggcgctc gtcaacggca ttcgcgaacg acgataccgc 48600 gccactgaac atgttgatcg ccaccgcaaa atcattggta gacttcgtgg tctggtcagc 48660 cagcttctct agctctttca tggacttagt agccttgtcc tggtcttctt gtttcttggc 48720 caggtcttcg ctggtttgag cgccgggaac cttgtccttg tcgatgagcc ctgattcttc 48780 catgccgcga cgagtccccc acgctgccag gcgaccgagc agggcgccgg ggctgaggag 48840 ggataggata tcactgccaa cggtcgcctt cccgagcact ccatcttccc aacgggattt 48900 ggtgtccttc gcgaagcttt ccacttcatt gggaatagcc tggactatct tgtcgatgat 48960 ttcgatcagc ttggtgaacg caggcgcgag cttttcgccg actcggtttt ccagggtagt 49020 gaacgtctgg ttgagattcg ccagggcatc gttgaatttc tggatgttgg actcgccctg 49080 gaccctggac tggagttccg cagtcgtcat ctcagtgact tttcccatgg ccgggccgat 49140 cttcgccagg gtgctcaggt aatctcgcga gacgccaagg gcatcagcgt aggcagaaat 49200 ttcgtccggc ttcagcttgg ccattttcgt ggccagatcg gtgatgatgt cgttgagcgg 49260 ccgcatgccc ttttggaagc tcccgacatc gacgccggcc atacgcagaa ttcgcgcttc 49320 cgggccgact cgcccgatat cgcgataagc acgccggaaa gtgtctgcca gatttttggt 49380 catctccgcg ccctgctcgc ggctgatggt tccaccggac tggcgaacga attttctctg 49440 gtactcttcc aagcgtgccg gggcgatgcc gatgtccatc gcctggatgc gctgctgatt 49500 gtactggtcc ctggtgttca tgaacgcctt gacgccggcc gcgaccaggg ccacgccagt 49560 ggcgcctatt gccagttgcg cgttcattcc gcgaattgcg ctcgtcacag aatcaatctg 49620 cggaacgact ctgccgagtt cggtggccgc gccgtctgcg aagtggcgca aatcctgaag 49680 gccactcgtc gatgcgctgt tcacgcgcct gatctggttc tggaggcgct ccagattgcg 49740 ctcggctctg gcagtatcgg cctcataccg aagtatgaat tcatccaaat cactagacat 49800 gaatcactcc ggcttgttgg cgagtccttc ggcgatcttc attgctggac caatgagctt 49860 ggacgcctcg gccagaaatg cgatggccat ctgcgatccg acttgttccc aatagtccgg 49920 ccggtcggcg tgcgtggccg ggtcgatgcc attgtgcttg agaacagagt tgaaaaccag 49980 ttccacgttc ttccagtggc cgaggtggtt gttgatgact gccgcggtgg tcagcggaat 50040 gccggcgtca tcgtcgccaa gcagcacttt cgcatagccc aggatttcca tggtgaaaga 50100 gcggcggaag tcggaatctt ggctgacagc aaattcgacg aaacggcgct ggaggtccca 50160 gccatccaat gccgaccacg cctcgatttg tacgcgagtt tgacggccat cgggaagatt 50220 gatttcaagc atgatacatc ctcagaagta gctggtcacg cgattatata gcgattttgc 50280 ggccgaagat atcgaatcgc cgatggcgcc caaatccagc aaattagcat cagaaagaga 50340 ttgaatctgt accccataag tcggactatc ttgagggaac gcaggatcga attcattcaa 50400 tactggaggc tcaacctgct cgaattccat attgatctca gccgcgttca acatgtctgg 50460 agactgatct acatcgagcg ccatgatggc cattttatcg gccaatatcg acttagaagt 50520 gatagcgaaa gtcgaggtgt tatcattgaa agcgttcatg atactttcaa cggtggacag 50580 gtccggacag atagcattga tgcggagtcg caccggttgg atgatctttc cattcttcac 50640 atcaatgtcc agagcttcgg tgtacacttg agcttccgtc tggtctttcg tcgccagagg 50700 tttcgacact acggaagccg gcgagtaaat ttccactttc ttgacttgaa gactcttcca 50760 gacaggaagt ttggtaacat cattgcgtat ggtgagagta ggcgtgttga gaatagactt 50820 gaggaaagag ttcaattggc acctcagaac aagtctgcgg cgttctggac gccgtttact 50880 gcgtagtcga acagatcgcc ggccgagcca accacgtctt cagctagggc cagccctcgg 50940 tcgatcatag aagagtcccc tgcatttctg aacattatag gcttgggatt ctggacgaga 51000 acttgggaga atgtcagccg cgcaggagtc gccgatatca tatccggagt ctgattgagc 51060 gcttcgctgg tacacatcat ccgttcgaat accatgccgc gagtgatgac tttgtacagt 51120 gtgtcgcgat ccaggagcaa ttgattgatc tgatcgacga catcaattga agggcaaaat 51180 acttcgacga tgatttccat agggtggatc gttctggaat ccatcttggt cgtaccatct 51240 tccagcatgt ggcgttgccc tacagaagaa aaccgggtgt tgacccggct tatcctcaaa 51300 tccgcagcaa ctagctggtt tgtgttttgg tccacaatcg aaaaagatcg cgaacttagg 51360 aggctggtga aaatccccaa catcagacca cctccagcac cgattggata acgttagaaa 51420 tggcttgacg cgcagtctgg gcgccaagat agctaccgaa aacaaaagtg tacgtgttgc 51480 ctttgcgtcg tccggtgttc tgtatggtgt cgatggccgg acccttgatg atagtcccat 51540 tggacagaac ggtgcggccg ccatcaggaa gagtggccac gagagtcgtc atatccggga 51600 tgctgcccgg aagaaatctg aatgatccct ttttggaatt gagaaggatg cgaaggttaa 51660 tatcatcctc gctccctgcg atgacggata cagatacttc cagaggagca gccttgtcaa 51720 aggcgaatag gccgccgtca taaagcatct catatccgaa cggctccagc tctttggagg 51780 atatcggact ctcatcatca gcgaacttcg acaaggaaaa ccccatcggg aacgatgagg 51840 ctgaaactat tacaattcct gtgccgaagc cgctgacgtt gatcatgtcg agtccttact 51900 tgctggtggt tttgcgagag gtggccttgg cgggagccgg ggtttcctct tcagcggccg 51960 gcgaggccgt ttcctcggcc ttttctaccg gggctgtagt cggggcttcc tcggcgcctt 52020 tctcgtcgcc ttggcctgct gcaggagctt cctgggcgcc ttccggggcc gattcggccg 52080 cagcagcatc ggtcgatacc ggagccggga tggttccgcc gttgtcgaca ttggaatcga 52140 cgtttaccgg gggaacggga agaccggccg gcgaggagtc gcccttgtcg gtgttctttt 52200 cgcggtccag gccttccaga tcttcgacag acgggttaaa cgagggcagc gggtccaggg 52260 gcggcggatt tttgccgtcc agaaacagtt gggtgccgtt ggcgtattgg atgcggatgg 52320 tactcatttc aaactcctgt ggtaacaggc ccgtggatgg tgatgacttt cgcatcgacg 52380 ccgaagactt ccccggtgat gtcgatgtcc agctgctcga tgccggtcac atccggcgag 52440 gacaaaattg catccgcgat ggatttgcga gcgtcatcat agcttttctg cggcgagaag 52500 atgtattcga aatatcccac gccggagttc acatcgaaaa tattttcgcc ggtgcgcatg 52560 agcatcgccg cccgaacgtc ctgggcgcac gcttcgacat ccctgaggat gaccatgttt 52620 ccattgtcgt ccaaaaggat atcattgttc gtcccggttc tgatcgttga tgtgctcatt 52680 ctttcctcgt ggcgagcgcc tgatactctg cgaattcggc gccgtccaga tagaacaggt 52740 tgattccgtc gccgaacaac gtccaatcgg cgtcgcggtc gaagacgaaa ttgccatagt 52800 caggtcggta ctgatggctg tactggagaa gaggaatccc gccgaagcag cggaccccat 52860 ggcaaacgat cacgccgtcg cggctgatat cggcattcat catgtccatg ttctggtaca 52920 ggcgaatctt ccaatagctg ctaccggcgt taaatgagat cgcttgattg gggactgctg 52980 tcagcggaat tttcttcatc agctagtacc ggctttgatc actttttcaa atcggaaccg 53040 atacggcttg gtcttcagac ggccgacgct tgccaccgcg ttgatcagaa cgccgtcgat 53100 gggggtgccg ttggtgcagg tgattttgct gccgtccggc atcgccacga ccagaccgac 53160 gacatcacga gcgcccgact tgtcctttcc ggtgcggttg gcatccagca ggactgccag 53220 gttgcgctcg ccctcggtat tcggaatgac gttgacgact acttccagga tgttcgcccg 53280 gttccaaact accatgtcac cgttgagacc gacgccggta tcggcagcgg tgaacggcgg 53340 gctgtcgatg ggatcggcat cgtcggcgaa ctcggtgacg gtgaatccgt tcgggaaagt 53400 tctgcttgcc gtgaactggc agatcgagcc gaacgcagaa atgttgatca ttgcttattc 53460 ctcactccat ttatggaagg tcgcggcgga tcgagtccgc cgcaaaccat tagatcatca 53520 catccgaccc ttcgacgaag cggatggcat cgcccttcga atagatcagc gtgtagttgg 53580 ccttccactc ggtcaggcca gtgttgctgt tggtatagct ggagaaggtg atgttgatcc 53640 agtaacccag ggtttggact tgacgccagg cgcggcgatc accggtgact tgggtgatgt 53700 actgctgctg gacggcgctg atttccttgc cgtaggtgaa cgtgccgttg gcagtcgcct 53760 tgtccagaac cggctgcagc accgccaggg tcatcgcctc gccagtgctg ctcgccggaa 53820 ccgcattgac gttcaggaac agatccagga gcgcttgagc gatagccgac ttcagccaga 53880 tttcgttggc atagacgttc atgtccaccg catcggtcgg accgccgcac agaatgccgc 53940 gctggtagaa cgcgagttgc tggccattgg cctgggtgac gccgatgtag ttgccccggc 54000 tcttgtcgac ggtgttcgca acggtatcgt cggaaacggt gatgttgcgg ccagggaatt 54060 ggtagtacat gtagttttgc gaagcgcccg gctcatcgta gttggtggcg gccagaatct 54120 cactggggca ctgctccacg aagtcgttgg cagcagtcgc cgacagcacg ttcagggcgg 54180 tcccggcgtt gccattcacc aaggtgaaaa gagtgccgag gttcgccagg gaagtagcga 54240 ccgtgtagat gaactggttg ttctgagccg cgttccaggc cgacacggcc ttgatctggt 54300 cattgtcgag cggcgcaccg gcgaacagga acgaaccgaa gttgttgctg acattggtgc 54360 tcttggcaac ggccgcgtcg ggaagatcgg cagcctggcc ggcgacgttg acgacgttgg 54420 aggtggacca gccgagggca gtggacatgt cctgggggtc ggcagatttc gccacggcca 54480 gaacgccggt gccaatggtg gcgccgacca aggtgaactg gttggtgttc tgattccagg 54540 taacggtagc ctgggccagc tgcgggtcag cgttcttgcg gatttcggtc tggatgatcg 54600 acgccacgtt gtccatagaa gtcgcggcgg acgtatcgat ggcggtgatg ttctgttcgg 54660 ccgcgccgac catgatggtc agaacccctg ctgagaagcc ggcgaaatcg gcgatggtct 54720 tcggcagatt gtcaccaaca accatcggcg cgatggcggt gtttacccag cgagcgaagc 54780 tgatgctgga cggcgaattc acgcttttac tgatgaattt gaaataagcc gcagcccgct 54840 gatactcttc tgactgcgcg ccgaagtatg acaggactgc gttggcgttg tcgaactcga 54900 tgacgattcc gggcgggatg acgttgttgg tagtcatgac gcgcagaatc agctttcggc 54960 ctgcgaccgg agcgcctgcg cctacgcccg aaatgatccg gatataacgg ctctgactga 55020 tcactggatg atctcctggt tatgttactc tgctgctaat cgattgaagc atgtgcgccg 55080 tatcgaccag cggtctgttg aatccctttc tcctgaccgt agatgctgag ttagccaccc 55140 atggcccggt cctgatgctt ctggctatgt atccttccaa tgccaggccg atctgggcaa 55200 gagcttgatc tggagtgatc tgtcctctgg ccagcctcat ggctatccgg ttctggattg 55260 cggcgcgatc tgcggaaaac agattccaag catatcgcat aaacggtcta gccgggatgg 55320 taattctgtg aggcttagtc acctcggttt ctcccggaaa gtcgtttctg acgaaccgaa 55380 cgccaacaaa ccggccccga acaatggcgt ccctaatata cctggtcccg cccggatggt 55440 cgatagttcc gccgtactca ttgagacgtg cgattctcgc gacttgtatt ccgaccgatc 55500 cgcctgcctt gtcaggatat cgagccgtgg aataccatcc ggctgaaacg gacctgccgc 55560 gcatggctct taacatctgg aggtgcgcgg cgattagctc tgaatcgcgc ctcagactca 55620 tatgcctatt aataccccat cggccgaata tgctgcgttt tcgtacaggc gaatatattg 55680 gttgtaagtt acaaccatgt caaaacttgg gtggaattcg aactggtgat tgtcgttctc 55740 gaatgcttcg ttggaaattt gagacacgcg aagaatgagg aagtccagtt cctttacgcg 55800 ctcaatcgtg gatcgagctt ggaaataagc cctcacatag ttggcgatat cagaagccgt 55860 aaccacgtga gttatttcag gattctgcca atgaagggaa ctgatctgga aagtcgtctc 55920 tacatgctgt cgagttattt ccacatattt gcgggccgtg ttgtccaggt accaatcggt 55980 ggcaggccag ccgcgaggaa tgtcaaacag tttctggaaa aagatggtcg gcctggttga 56040 cgtcccctgt tgggtcggct gagctttctg gacgacttca aaatccggga actgcaaagc 56100 ctcttgagca gatgccatcg ccgcattcag ctcgacaacc attttcgcta tcagttcgcc 56160 gtcaaacata caccacctag aaagtcggtt tcccgtcatc ggtgaacttg gccgcaccga 56220 tatccacggc caggcaaact ccccagccgt cctgataaaa ccaggagcct tgagactcca 56280 gctgaaaaac tcttccagtc cagaggaact ggtcaccggc catattgcga tccaagtcaa 56340 ccatatcaaa gttggcgaag atcataacat aattccgttg gaactccaga ttaaactggg 56400 catactgatc gcgtcggact cgctggacag acgctgccag gtcgaaaggc tccccgaaca 56460 tggagacata ctgggcttga tcattcttca ctcgctgctc aaacttgcga tatttcacaa 56520 tttgagtacc gatgaccccg aaggccattc gcagaagatt cgcaccaggg atcaccagaa 56580 cgtccctcca accttccgga agcctcggcg ctctggaaga ccgccgatgt agaatccgcc 56640 caccgctttg acgctgagga gcgcccacaa ctcttggcca taaggcgtcc cggaaagcca 56700 ccactgccaa ccattcttgg ccgggggcgc gagcttggcc acgctgacct cgccgaccgt 56760 agcgctggtg atgaaacctc cttgggttcc accggcagtg acgccacctc cagccgcgcc 56820 ctgaacttgc atcgtggaca gcgacaggag gtgggcggtc agaagataca aacaggcttc 56880 cagggcttta ccattgagaa tccggtatgg cgaatcgcga tcagaaatga attcgcacgc 56940 aatgtcgaaa tacatctgca ggcgcacgtc cggataagcg actggatcag caaactccgg 57000 aaacagcgtg cgaaacttat tttcgtcgaa aatcaccata ccgaaaccct cggttaaatc 57060 cggaactctt gttcctggga agcgctggcc gtggtcacct tgattttctg ctgcaggcga 57120 gtagcgtcca gaggctggaa tccatcgcgc tccatggtgc gagtctcttt ggaaatccgc 57180 tggtggtcac tggtgatgtc tgtcttcacg actcgcagat aacccttatc catgtgacgc 57240 atgaaaatct tattggcctg aagcagctcg aaatccgaat cgctcacggc agtgcaatcg 57300 ccctgcgggg tccagatcgg acgcccggcc gcgtcggaaa tcatgtcgcc gaagccggaa 57360 gtttcggatg caatgccggc gcggccacga atcagaatct ttcgctggag gcgaggattg 57420 gacggatcag aggtgtcata cgcattgtaa gacacggatt gagtcatggc ggaaacgatg 57480 taaacagtca ttggcgtagt cctagtaatt atgccctaac cggcccctac aaccgagtca 57540 gagtcagagt gaacaaaggc cggaaacccg gcctttggtg aataggcatc ggttagatgc 57600 cgaggtagcg caccacggcc cacggacgct tacacagcgc accagcggtg ccgttggaga 57660 agtcttccac atacgacttc gcccgctttt cgacacccag ggtgatgaac ttgctctgta 57720 ccagctggct gaacacgctg ccgccatcgg tgcttccatc gacggccgcg ttcacgtctt 57780 cgacgaagag caccagagca tcttccggct cttgggcttt catctggacg cctgacagtt 57840 ccggagcaga cacgatccgc attttcggat aggtctgttc gatccagtca gaaaccgaaa 57900 tgccgtatgg cgtggtgacc gacaggtagt ccaccttgct ggtggccagg gccagggtga 57960 tcttttccgc cttcggatcg atctgatctt gactctgaat acgcagctgg cgaacggcct 58020 cgcggatatc gccgatgatg cctgcccagt cggcagtgga ccagccatgg ctcggcgggg 58080 tctggaacgg cggcaggttg ggatcgttca ggaaaccata ggtgcggttg cccaggccgc 58140 tctgccagcc ataaaagccg atggcgttgc ggaagatttc cagaccgatg gccgcctgtt 58200 ggcgtttggt ttcggcgctg ttcagccgga tggccgaggc acgaccctct tccagggtgc 58260 caaccatcat acccagctcg ccacgaacga tggtgcgacg ttcgaagttg gcgttccagc 58320 tggtcagcgg gatgttggtg tgatcgccgt attccaccgc agtgccggcc ggctccacga 58380 tgccctggac gatttcttga tcttcccagg agccaacggt atcgatgccg atgatttcgt 58440 cgatcttccg tgcagcggtc atgaccttca cgaagcctgg caaccaggtc tgcaggaact 58500 ggatgggagt cgggatggac ggcgtggtca ccggggcggt gaagttgctg tccatggccg 58560 agccggagcg gaacgcgccg gccttcgcca aggccttgat ctggtcctgg acgacggcgt 58620 gatcgaatac caggccgatg cggcgcagag acgccacggc gtcattggtg atgtttttca 58680 ggtcgaaagg tttcgcattg cggcctgcga ggcgcgaatg ggtcttgctg atctggctca 58740 tgacgcctcc ttactgcgtg agctggacga tggtaacgcc agcaaccaga ttccccgccg 58800 actgggccgg cagactgatg gcgttaacga tgcgtgcgtt gggaatctgg accaagccgg 58860 tcggcatgga gccggccttg aagcccacca gggcgcctgc cggcaggcca agcgcgttgt 58920 cggcggtagc caggttgttg gggacatagg cgaccaggtc accatagtcc aggtccaggg 58980 cggttgcggc gccgttgaaa atttcgacga ccaggccggt ggccatatcg aagaactcgc 59040 cttcggcgcc atcgggcaga tcatagctgg gagccaggga gtctccggcc gaaccgaaca 59100 gagcatagtg cttcggatga ccgaggacac caaagaagtt ggcgccgccg atcacgactt 59160 cagaagcacg agccgcaatg gtcttcggct gaccttcgcc gagggcgctg acgtcaccgg 59220 cataaccgaa agcgcgactg atgcggttgg ggccggtggc ggtggcagcc ggagttacgg 59280 ccgacagagc catgattcga cccggccgcg cccgcttcgg gccgtcctcg atcagatcgc 59340 ccggaaaacc aggagtgtac tggcggtaaa cttgtttctg gaacatgagt tactccccct 59400 tcaggtagct gtccagctcg gcgcactgcg gagcagaacc ggccgaatcc tgggctttcg 59460 attgacggct ggccgcgccg cgcgaggctt cgacgccttt caggtacatg tcgagcgcca 59520 gagcttcctg gcccttcgca cagctgatgt tcagcttttt cacgccgtaa acagcgactt 59580 cagccgagtc catagctcgg tgatcgaacg caccaaccac ggagctaaga cgcttgtaga 59640 ggcgatcttt agcagcaatg tcgcgataga gaccgcgaat tgcagcatct tgcgcgttct 59700 tctgtgccat ttcaggaagt tcctcgctgt tatccttgct ctcaccacca tcgtcgctgg 59760 cggtttgcga gccgctgagg ctgctctgct cctccaagcc ctcgacgaca tcttgacctt 59820 cgccatgctc ttcgtctgcc ccttcggcta ccgtgccctc cagtcgagcc agaatggctt 59880 tgacctgaga gatcagttcg gcgacttcgc cttcaccgga catttcggat gcggcgcttt 59940 cttgatgctc cggctcgacg gcggccacgg ccggatcgac aacggaaggc tcctcttcct 60000 gctcttcgtc atccttctga gcaccttcca gagtcggatg ctcggtcagg tgctcgctgt 60060 cggtcggttc ggccggagct gcgccttcct gatgctccgg ctcctgctct tcttcgccca 60120 ggaacttctg gacggacgca gatagcttcg gccacagggc gcgcaactct tcgaccgccg 60180 agtcagcagc ttgccctacg cgctggacag ggggcttccg cttggctttc ttgagactca 60240 tttcattacc ctcatcggat ggtctgaaat caaaactgag atggtcaaaa cacagaccat 60300 ccaatactct ggcccccggc acacgaccct cttttaccag ggcaatgtgg ttgccgcgca 60360 tcttgtcctg gacgacttca taaggcgttc cgttccagat gccgggttgc tcagtgtagc 60420 ggcaactata gcctagggac aggtcttctt tgcccctttc cagctgattc tgcatgttgc 60480 gggaatagat gcggatatcg ccacgtgccc atggggcttc gtagtaagcg ttggatgtga 60540 tgatgccctc cacccctttg tcttcggggg ccacgctatc gtcatcatcg tcgaatcccg 60600 acagcatctc atgctcgtcg atcaacggga gattcttcag agattcgatg tactccggat 60660 cgctgacggc agactccggg cgatatacgt tgacaatccg cgtcggatcg cccggaagac 60720 cgagttgacc agcagaatat tggaaaacgc cataagagct gatcgggcag ccctctatgg 60780 tcatatatcc attttcgtca atttttcttt tcgactttgc catcgttaat tcgaagagtc 60840 gtggactatg gctgtattat atacgcagta catctaaggg taaataagcg gaacaataat 60900 tagatgtagc cgcgactgtt aacttacatt ataatttgta ttgtgatcta attaccagtt 60960 tcctcagccg cgaaatccgg taatttggtc tcggaaactt gacgggattt gtctaagcct 61020 actgccgcga ggctttcaac tcctaaaata attaaaatta ccaatttacc gattaaaaat 61080 tgaatttcaa tacgtctaga gtatatagat tgacgttata ttataacgtt acttatagat 61140 gaattctatt ggaacgttac ttctaatttc ccaggctata tacttttgaa gcatgcggct 61200 aaatcggaaa ttaggaactg gctctgttaa agcctcgcgg cagtaggatt tccaaattac 61260 tgctattttc cgtaaacggt aatttgcggc tatccggact agaattttta gtcagaatcc 61320 agatttttct cagcattatc ggccaaaagc catcaagatg gcgacgccga tgattgccaa 61380 atcgatggcg gcaaacttca ggctgaagaa tccgccgtga atattggccc tgattacatc 61440 gaccacgagt cggcgccggc acgtcttgcg gttcatttca cgagcctcga cagagcgtcc 61500 accagggcgc gaagatcggc gacgagctca ggcgaacaat ctttcgccgt cttccctttc 61560 tcactgcgct ggatggaata agcgatggcc gcagcctgct tcgggtcttt accggcttcg 61620 atttcccgct tgatgttttc agaacgagcc tcattggaag tgccatgaac taacggcata 61680 tagcgctcct atcgatatca aatgatcggt atctttctgc acctacagtt aatcgcccat 61740 cctggcggcc cctggtctgc tttcggaccc tcccaaagtc tggggtcatt cagcttgaac 61800 ctcttcccat ctttctccag gtgggtgtgg cgaggagtct tgccggcaga agagtgtagc 61860 cactcgaact cctcgactcc attttccgcc attctctcat cgctcagaga actgtaaagc 61920 ttgcttgttt gatctcttgc gatgagttcg attcgatctt cagaaaactt cccgactttg 61980 cgaagtgcgt tagttatgcc ggaagttcct tgctcttccg gattcgggga agtcagagac 62040 agcattactg atgtgtaaat cttctcgtgg acttcctctt ggatcttggt gatgagagta 62100 tgattgtaag tggttgcggc ctccagggtg ttcctgacgc tctcattata cgcagctcgt 62160 ggctgatcga cgccggccac cgacaagctg tgaagggtcg cagcagtggc ggcttcttcg 62220 gtccggttga cgaactccgg ggcgatcttg gccgcgaaac cttcaaaaat gcggctccat 62280 cgctgctgta ggcttcgaag ggtcatcttg aacaggacgt taacggattc gtctctggcg 62340 aagaaccgtt cggccgcagg ctgggacagc gccttctcaa tctcgtttcg atagtcggag 62400 atcatgagct tggacatatc ctttatctgc tttcgatacc aggcctcgat tcctgccgat 62460 ggaattatgg gcttccctct tccaactgga agaggtgccc ggcgctcgcg ctttttggag 62520 gccttgaatg ccatcactcg cccccgaatg gtttggtggt gtcgccgttc gccagccagc 62580 gacggaaagc gggcaggtca acttcgtgga tggagccgag accatcccaa cccggacgga 62640 agcaggacag atatccagac ttcgcgtcat tgatgttgtt gaagccgagc atgcatttgt 62700 gctcgtcaaa ctgcccttcc ttgttcacct ggttgacgac gaagacccgt ttggagccca 62760 gattcggacc gacgaagcaa tcgacttcat ccccatcagc gcctttcgtt cccttgatga 62820 atccgtagtg atgtttcatc tgaactcgcc agctcccatc ctttccttgc cgaatgcttc 62880 cacgcggatt ttcgatcaag gtggttattc cattaacctt gatcctttgg agttccgaat 62940 gatcacgagg accgacgatg cggttggacg aaaacaccga aggttccatg cccgacacgc 63000 caggttggga cgtgcgcttc aggccaggcg cgtcattgtg ctctatgtct acgccgtccg 63060 gcgcctgaat gtcgtccaga tcttggagct tcgacaaaag atcggccagc aagttccgta 63120 actcggcctt ggggtccggc cgcgacggcg gtgcagcggc ctcgctggcc ccttcctcgg 63180 ccgctttcgc gaggggctta gtcccgcgtg gggctgcggg aactggcccg cctgcgccct 63240 ctacggcgcc cgcttgggct tcggctcgct cggcttcgcc ttttgccttc gccgactgtg 63300 caccagcctt ctcgaattcg gccaggtttt ccggagacat gcccggttcg gtttcggcct 63360 gatcgtcggt gagtcggttg tagccggaac gtggatcgtc acgcagacgt tcgcgaactt 63420 catccggaga cacaacgccg gagttgatgt agatttcgtc ggtcgcggct ttcttgttgt 63480 tcaaatcggc ttgttgctgg ctggtcgtgg agtccacagg attccagacg atttccagct 63540 gcacatcgat ttcttccgac ttcgccagaa gcaaatagtg gcgttcgaga agtgggtcga 63600 atatgtgctc ttgaatggac tccagttctt cgtgataaga aatcgtttcg tgctcaccag 63660 tggcattgaa tccttttgga gaagtgccga ggagcttcgt ggctggagtc ttggcgatgg 63720 ccgcgaccag ctgatattgg ttcatgatga tgctgtcgaa gtcggccagg ttcgtgtcga 63780 actgctccat gccttcgtca attcccagaa ctttcacgcc gtggttatca cggttggcga 63840 tccagaacgc caggcgagcg ttgaaggcgt cttcattcgc gatggctttt tccacgtcaa 63900 cgtgaatggt actggtccgc ttcgacatgg ccagcagcgg ggcttcgttc gccgtccgtt 63960 ccgccgcata cacgcgctca tagattctct gggtgagcgg gatgccgccg aagagatatg 64020 tgggcttcag gatatctggc ggctgcggcc cgcgaacgac taccaggtgg ctgcggtgat 64080 attttttccc gctgatgatc cagaaatccg gctcatagaa atgttcggca gacggatcgg 64140 ccgtcgaggc agcggtaagc tgcggcatcg cccaatatgg atcgacctga gagattccct 64200 tgtaggagcc gggcgtgatg ccatccggat tgaacggctt ctcataatag tccggatcgt 64260 cggactccac gacgaacagt gcgatacgaa cgccgaagac gtttttgaaa cggttcagtt 64320 cgacaaggtt gtctttgacg cggaactcca tgtcgcgccg ggcgatcagc gcgctttgtt 64380 catcggatag cttccggccg tccgacttga gttcccatcc gttccgtgcg gcgtcttcgc 64440 cggacatgga acaagccttg tccaccaacc agtgctggga aatgatggcg caagcttggt 64500 gtccgatgaa gccttgggag ttataccaat cctgcagcat ggtcgggacg acatagggat 64560 tctggccgcc cgcagcagcc ttcgcggccg gagtcggtcc gtcaccatac gcgctgtcca 64620 ttgcgacgga taggcccggt tccagaaaat ccttcacgct acggatgacc ggggttttct 64680 ccggctcgac gttccagccg cgaatccttc ccagcttgat catggggtcg agcggatcgt 64740 gttgagggat ttgtgcgact ttctccggcg ccgattcaga acaggcagca ttatcctttt 64800 tgcgcccgaa tatccaggaa agtttaaaca ttgtagttcc acgtggttgt tggctgtgtg 64860 cgcttattat aggggaaaca tcaaacgttc aaaagagatt caaacatata catcagatta 64920 acagttgcaa ctaatcagtt atgagaaaat tattctttac gggaactttt cggcagatta 64980 gactctaatt atcaaccaat ggagattaaa catgaacact cttttgccaa tcgtacatat 65040 cgtgttgaaa gacggcgaag ttctgggcgt attcgattgc gacaaatcgg caagattgtt 65100 tcgcgacatg aaaggcggcg tgctggattc ctggatggtg gaatcgcaga acagctcgcg 65160 ttcacgcctc gtcacgaaag aaagctatga agtcggcgat cacgtcatat acctggacga 65220 gcacggagaa gggcacggca aggttctggc ggttgagccg cgaggcgagc gagctgtcgg 65280 cggacgggag ctgtacaacc tgtaccaaat cagcagcgac gatccgtccg tggagatttg 65340 gatgctcgac gcagacatca tcggcattta tcccgacgaa aagcgcttta ctcctggcga 65400 gcagatggaa tagactctgc tcatcaacta aagagggtga cgaaatggcg agtatcaccg 65460 tatggattgc tactgcttta ctttgcactg gagacggctg cgtccagatg ccggaccata 65520 ctagcagacg gttcgacagt aaggctcagt gcgaagacgt catgctgaga gcgattgata 65580 agatgtggga gcggcaccaa ttggtcgtcc aggccgtttg cacgccttat ttcctgagta 65640 gcactgagac gcccggattc tacagtccgc cgccccatcc accgactggt ctgaaccaca 65700 tgtgggacaa ctgggttcgc ggcggcagtc taccatccta tgaaccggga agagggtgga 65760 gcgaatgaag ccgcgccgtc cggaagttcg ggtgagcctg gaaaccgccc tctggatgtc 65820 gacatccgct gcactcctcg cggcgattat cgccggcgcg gttttccctt cttcgacgat 65880 tcaatgtccg gaagaaagac cgcctgcggc cgagcgcttc caccatcctg aaaacagcaa 65940 attctttcct cacatacaaa agggatagtg agtatgaagt atgtagtcct gaagatgacg 66000 gtccgtggca tgtcgcgtga agttcctgtg atcttccccg acctcataag tcatgcgaac 66060 atggccgcga gtgcgattgt ggcccttgat gctgagtgcg aaggtttcaa gaaggccggc 66120 gacaaagttg atatcgtcgc agcatcggca ggattcctgt cttcgatgga tatcgatgcg 66180 aaatgctacg gccagtcgga ctctttgggc ggtctgaagt cgagagaatc agaggatggt 66240 gaactcatcc gaatgatcga ctatacccat ggttacgtcg gttaaggcgc gctgcctttc 66300 ctgcgacaga cgcgccgtcc tggacgaacg aaaactaaag tcgaagcgac cgccaatttg 66360 tagatggtgt ggaggatcga cctggcgaat agtcatggaa gttacctgtt atagttcgtg 66420 taggccctat ccccacaggg ctggctcggt cggatgcatt ctagaccgat caggctcaac 66480 aacaa 66485                          SEQUENCE LISTING <110> Optipharm.CO., LTD   <120> Novel Pseudomonas aeruginosa specific bacteriophage PA4 and        antibacterial composition comprising the same <130> OTP 1.29 P-1 <150> KR 10-2016-0177044 <151> 2016-12-22 <160> 1 <170> PatentIn version 3.2 <210> 1 <211> 66485 <212> DNA <213> bacteriophage PA4 <400> 1 tcgtcgagct tcctggagtt ccagacgatt tccctttctg aggtaaatat ggctactaag 60 gccgatttgg aattgaaagt tcatcagctt cgacgagtca tcaaatctcg cgagcaagaa 120 cttgaagagt tggaagttcg atcggagcgc catcgcgaac gacggtgctg agcatggatt 180 caagatcaac agcgacattt actaacagca acctggagaa ccaaatggat attcaaaacc 240 cggcatgaag cagtaaacct gggcgcaggc aattcgccga ttcccggcgt cgaatcgctc gactggccgg 360 actgggacgg cgccagcggc cgagtgccgt atgaagacgg cgaattgacg gcggtctacg 420 catttcactt cttcgaacat ctcactggag cccaggtcat cgatttggtg aaagacctgc 480 agcgggccat ggcagtcggc gcgacgctca atgtcgttgt tccattctac aactccaaca 540 tcgcccacca agacctggac cataaaacgt tcttcactga agagacatgg cggaccctgt 600 tcagaaatcc gttctacgac aagaacaggg aagacccttg gaagttcatc atcggaacca 660 acgtcatcat cggcgtcgcc gagcggaacc tggcagtcat gtcgcagttg atccgtgtag 720 cctgaccctc tgcgatccga cgaacggtag tgcgaaagtg ctaccgtttt ccatttctgg 780 cgtatagtca acccatcgaa acgaactttc caaacaggag aatcgatatg aacgcagcag 840 agaatctgtt caccggcttc gaagacctgg gtgacgactt cgctaccgta gcgatcaaca 900 acgaagcgcc gaagaccctg gaagacgcgt ccatgggcgc tcgcccgaat tcccggaagg 960 aagtgaagct gtatcgcgac aagtgcacca aatgcgcagg caccggcctg taccgtggcc 1020 cttcgtctta tggtcgcgcc tgcttcgcct gcggcggtgt tggatacaaa gagtacaaaa 1080 ccagcccgga gcagcgcgcc aagagtcgtg ctaaggcggc agaaaagcgc atcgagaaaa 1140 tatgtagcgc tgcgcaagag cgcgacctca aaattaaagc cttcgaagct gcacacccgg 1200 acatcgtcga gtggtggact ggaaattcct tcagcttcgc tcagagcctt caggagtcgt 1260 tgtataaata cggctccttg acagaaaatc agatcgctgc tgcgaagcgc gccatcgaaa 1320 acctcgccaa atatcgcgag aaagtggccg cgcaggaagc tgctgcaccg actctggaca 1380 tttccggcat cgagaaggcg tttgagaagg cgaaagaatc tggcatcaag cgcccgaaaa 1440 tccgcctggc tggcgaaggc gaggagccgc tcatcgttat tgtgaaagag gctagcgctc 1500 acagccggaa cgccggtagc ttgtacgtct tgggcgacat ctacctcggc cggatcacca 1560 atggcaaatt catcaagagt cgcgactgca ccgacactga gcatgacgac gttctgaaga 1620 tgtttgaaaa gccgatggaa tcggcagtcg cctacggccg gaagactggt caatgctcct 1680 gctgcggtcg cgagttgacc aaccacgcat ccatcgaaat gggcattgga ccgatctgtg 1740 ccggaaagtt cttcggatga tctacataac catcaaagcc atggcctggt tcgccctcct 1800 atgggcgacc ggcttggcca tcgtaactct caccatacat ttatgctact gaggattatc 1860 catgagcacc gtccatgacc cgatgaagga caagatcacg ctgcacggcc tggggttcat 1920 tcaagtccag ctcccggcag ggcgcctcca tgtttggcac ccggagttgc cgcgccggct 1980 ttgcttcaat cactcggcca tccacgatca tagattcgat ttcgagtctc tggtactggt 2040 tggatcgatg gagaacatca actattacga ggatcgctcg gcttgcctcg gcgaaatgac 2100 tcacgaaggt tatgaacact cttcggctcg ccaggcttgc ggcggtcgcg gctggaatcc 2160 tgtgggctct gtatgtctgc gccagaggca aagatttgtt gttgacgccg ggcagcaata 2220 ttctatgtct gcgtacgttc cgcacaagac gaatccgctc ggtgacggcc gcgtggcgac 2280 tctcatgcgg aaaggcagcg ttcataaatg gcctgccact tcctatgtga cgctgggcgt 2340 cgatcccgaa accgacttcg accgctacca gtggtcggtg ccgacgctct gggaagtcgt 2400 caccgatgtc ctcggcggcg cagagttcca aatcccatcc atcccttgac cgaaggaacc 2460 aaaaaaatga agaaattctg tatcgacatc accaatggcc tggccggctt catcatctgg 2520 ggcggcgcca tcgtcctggc cgcttctgtc tttctcatcg gtccgctggc catccttctg 2580 accggagcct gggttgtgtg tacgtccgtc gtgttcgccc tctggttcgc cgtcgccggc 2640 atctacgaag agtcgcaaaa gcagaccgag catctgaaat ccctggtgtc gctccaggcg 2700 cgtgaacgcg gcatcggcta cggtccagga gatgccgttt gcagcgccag cgctccggcc 2760 gtccgtag agcccaagct cagccatccc aagctgaagc cgggcgcaca gctcgcggcc 2820 gccgtcttgt tcttcgccgc tctcatcctc ctgctggtag caggcgattg gatctggaat 2880 ttcttccagt caatgccgaa atagtggaag aaaatgcttt acttccattc tgaatgaagg 2940 caaaatagct ccattgaaac gcgaaaccct tcagacaaaa ggaaccgacc atgaccgacc 3000 agaacgaatt caccccggaa gccatcgaga aggcgaaaga ccgcatccgc aaactgactg 3060 ccatggcggc cgactcctcc agcccgcacg aagccgccat tgcagccgag cgtgtgaaga 3120 agctgaagga caaatatgac cttcacgact tcgaagtgac cggcgagatt cgcgaagagt 3180 tcgatgagca gatcgcgact cgttactatt ccgcaatccc gaactggatg aagttcttct 3240 cggtggccgt ggcgacgtac aacgactgca tcatggattt cgccggtggc atcaacgatc 3300 accgagcgac cgccaaggct tcttggcacg ccgcaaacgg cgggactacg aagcgctggg 3360 gtcatgccgt ccgctttaaa ggctacaaat cggacgttga gctggcggtg aacatgttca 3420 actcccttgt cgaagcggtt gatcgtctgt gccgggagta tcagaaggct caaggatacg 3480 gacgattcaa cgtcaaggtt gccgcgcaat tcaagctggc cgcgacccag gaaatcagct 3540 atcgccttca ggccatcacc aggaagcgca tggagctggt atcttctgcc ggaacgtctc 3600 tggttgtggt gaaggaagct gcggtgcacg aacatttcgg cgatcctggc tacaagaagt 3660 caaatgttac caagctcatg cgcctggacg atagcgacgg tcggcgcgcc ttcaatgccg 3720 ggaccaatgc cgggcgcaac ctggaaatcg ttcggtctgt ggaggattga tcatgagctt 3780 ccctagcgac aaagttatgc tgcgaatcgt ccaatccatc ctcgcgatcc tcatcgggat 3840 cgcttgggcc tgcgccgact atggagtcgt ggccgccgaa cttcctccat cgctgcaggc 3900 ccatcccgcg aggccagggc acagcgaagt ctcggcccgc gaccctaggt cggtcgaggc 3960 cgaaaaagcg cgggaagagg ccttagaata tgtcctgtcg ctgcgcccgg aagttatcga 4020 ggcgaaagct cgtttcgcgg ccgaggcggc gcagcaaggg ctgtcaacca aggagtacgc 4080 tgagctgcag agccgaacca aaatactcac aggaacgcta ttggcgtttg cagccttctt 4140 gttcatcttc agcatcatgc tacccaggct ttgaataggc ctgggtagac cacaaacccc 4200 cagccaaaag agaattacca tgaagaaaga accgattcgc ctcaactcca tggcctcggc 4260 ccgatccatc gatgcggaat tcgcattccg gatggacgag ttcatggctc gtgtagcgaa 4320 agagcacgaa gcgctcgcag ctcgcctgaa tgccgagcat gtggcgctct gggacgaaat 4380 ccgcgctgtc gccggcctga gcgctgccga cttcccgaac atcgccatgg cgcacgacac 4440 ttccgatggg aagctctatg tcatggatgc cgacgagttg gagcgcgtcc gccaagcctg 4500 tccctgcccg gactgtgaag ccgctcgcgc tgaaagcatg ccgtcgcaag ccagtggagg 4560 gattcattga tggtactgaa gctatcttcc gttcacgttc ggatcgacgg gcctgatggc 4620 aaggtattgt cggaaggcca cgcagagttc tccggaacgg cattctggat cgccgcgcaa 4680 cgcgaaatgc agctcaagca tcttgtcgga acttccttcg aaggcgccct gacctacctg 4740 gccgacaatg gctacaacgt aacattcagc aaaggtgaaa agcgatgatc gaaagacatg 4800 tagtggatgc ggaagtggtc gagcggattc gttctcttcg catgcgattc aacgtcctgg 4860 acgaaaccct gcaacgggcc gtcgatatgg cgatgctcag ccaccagaaa tctctgcaag 4920 acctgcgcaa ctatgaagct cagctctggg atgcgctcaa tgcccgttac ggactgtccg 4980 tcgaaaagac ttatgacctg cggttcgaag gcgaagaagc cgtgctggtc gaggttccgc 5040 caggcgacgg ccaaggtgat gacttcatcg tcgagtcgga agccgaagcg ctcgcggccg 5100 gccaggaagc cctgggagtc ggcgaggccg ttgcgtcgac actcagcgcc aggaaccaca 5160 ccgagtaaga cccgaagccc ggagcgatcc gggcttttct atgtttagaa gtcgaagaag 5220 cctttgggct tccggatcgg cagaatggcc gacataatca ccgagtcagc gatgttcggc 5280 gacttgatct tgcgtttctc gcgcatatcc ttcttggact cgactttgaa ccggccgttc 5340 atgtccaggt ctttgcgcgg cgacgaaagt tcgatacaca gttgatttag tttgtccggg 5400 tgaatcgttt cagagttgat cgaaatcaat tcgtcgaagg gataaacctt tccatgctca 5460 accgcttcat aagtcttccg gaatcgggtc gcgacttctt cccacttctg cgccttgatg 5520 ttgctgaagt ggtctttgtt cttgatcgtc gtgtgcggca gcttcatgta gatatcatca 5580 ggcttatcga cagcgccgcc cgcgttgaat ggatcataga tcagtttgaa gtcgggactg 5640 gcatcgttca actcggcgaa cttcgatccg acgtgagcgc cgacaccgat ggagtcataa 5700 gtgaccgagg cgcctttcat cttcgccagg ttgtaaacgc ggctggacga cttgagcagt 5760 tcatcttcca ggccgtccca ttcgtccact tccataatga cgttgccgtg catgagcgta 5820 gttgcgttcg catcctcgcc gtcgtccgca acgtcgaagc cgatgcgctt cgatccggcc 5880 ggctcccagc cgagtttctt gtgggcgtcg atggccgcga gaatgaactt gaggttgatg 5940 acggatttgt cgcctccagt cttcggaatc cctccataaa tgtgctcggc ctgctcccgg 6000 tcgcgctcat aggcttcgtg aatcactttg agcatcgtct cactgaggaa cggattttca 6060 ttccagttga tcatcttgac gcatgagtct ttcgggggtt tgaccacgaa gttctgatac 6120 acgaaatcgg tcacttcgtt cgggttgaag atgatccaga tttcagagtt ttctttccgg 6180 atggtaggct cgatgacttc ccattgttcc tgggtcaggt agtgagcttc ctcaagccag 6240 agaatgtcga tgccttcggt ggacttgatt tccgacaggt tacgggcgat cccatagaat 6300 aagaattctg atcctgtcct cttgtgcttg atcgagttct tcgtgaaaat gaactcgccg 6360 ttgtactcag aattctcaat cttgtccttg atcaacgtgt agaccgattc actgatgcgg 6420 ttctggaact ggcgagcaca gaggaacttg agtctatagt tggccgcgag gtaaacggcg 6480 ataccgcctg cgtcgtgtga cttcgaagac gcccggccgc cataaatgac tttgtaacgg 6540 gcgcgagttc gccagaccgc tcgcagtgca ggattgagtt tgtacattta atcagtccat 6600 tgttcgcaat aggccgagta tatcgacacc gcagcagacg gtcgagcaca accgttcgtc 6660 ggtgtgcaga atttttctca ctcagacact ttacttccat tctgactatc ggcataatct 6720 cctcatcgaa acgcgaaacc cttcaaacaa aaggaagccg aaaatgacta agcaagccaa 6780 aatcctgagc gtcgctaaat tggccgtggt cactgaagaa gtcgccaaag catacctgga 6840 agctgaagag tggctggttg acgaagccgt gtacaccatc aaggctgagc gcaaagccgg 6900 cctgctgtaa cggaatcacc cgcccggttt gccgggctga cagccctgga gggtaaaacg 6960 atgatccaca ccgtgaacgg caagcagtac atgtacggca gcttttccgg cataaactcc 7020 aaactttacc gcctggaaat tcgccacggc ttcaccatgc cggtgcaggt cgaggtccgc 7080 aaaaacagcg ctgaatacaa gcgtgtttgc ctggccatca ctactggcgc ctaaccgacc 7140 cgcgcccggc gaaccgggct ccaaaactcc aaaaacagag gatcgcagaa atgaccaaac 7200 aagtccagat cgaagtcgcc aacctcgatg aagctttcgt ccagcacctc ctggcaggcg 7260 gccatctgtt cgatgtcgac gactatgaag ttgcagaccg catcctgctg aatgtggatg 7320 gcgaaccggc tatccagttc gaactgaatg ccgaactgtg gaacgaagag actctgggca 7380 ttccgatgga catcgacagt gacgagttcg ccgatgagct gcaggattgg gtcgagtcga 7440 aggtgaattt cgccttcgaa gagtggctga gcgcggacga aggcgaagag tgattacgat 7500 gcggctggga tggtcccggc cgcgacttct tatgaggatt gtgttatgtc tagcatagtg 7560 tacttccagt acatcaccgg caccattcag gttcctctgg aagtcgaggt ggaggccggc 7620 cagctgcaaa tggtcaatgt agaagtcgat cctgatggct tccgcaaatt ctggcctatt 7680 gccgatagtc tgctatggga cgcagaggag tgcaagtttc tgcctcgcta caaatccaac 7740 tacatgggtg aggccgtaaa gtatgccgac caggctatgc tcgctttcgc ggccggccaa 7800 tactacctgc ggatggggtc gaaggaagag cgtaaagacc cggacgccga tctgcatgcg 7860 ctggagttgt ccgcattgcg agcagaactg cgaaggacca aagtcgccaa acagcagctg 7920 gtgcgcgaaa atactcgtct tgtcgaccgc ctgcagaact tcgtagcccg cgaagacaag 7980 gtcgccgagc agaaccgcca gcttcaactc agaatccagg atttggaggc cgagctagcg 8040 tcgcagaagg ctcttcggga agagttagac aagagcctgg acggcagcat ccagaacgcc 8100 aacaatcagc acaagctggc gtgcgaagcc agggagcaga tggtcaaggc cagggaagag 8160 gccgaattct atcgcatcgg catgcagaaa gtcgcggcca tagccaacat gaatcctttc 8220 gaggactact gaccgtgcaa aagtacaacc tgtcccatat ccctcgccca ggaacgctcc 8280 agttcgaatt cgaatggctc gccgttaccc ggttcggcat caaggatggt gctctggcta 8340 tgtcgtccga tggcgagcgt tactgcaacg aacacatcga ctggctctgg cggcagttcc 8400 tgacttcaaa aggtttcaga taatctgaag aaaatgcttt actcaatgag gtgacttagg 8460 tatagtcacc tcattgaaac ggaacaatct cggagagaaa gcgatgccgg tatttaacat 8520 tgaccagtcc gtaactgtag aagctgaagt agaaaagggc tgtatctctc gcattgccca 8580 tctgtgggac gaagagggga atgatctttc ctgcaaactc ggcgcaaccc gagctttgaa 8640 tgtcaaagcc gcctgtgctt atcttgttcg cgatcctgcc gctaaggaag tgactactga 8700 atgcggcgta acaatccgtc gcggcaaagc ctaatccaac gcgcccgatt ctccgggtat 8760 caccgaggaa cgaaacaatg atcggcaccg tacacaaaga atccccgctc accttaagca 8820 cccgcatcgg ctccgcatcc ggcgagaaac atacctacac aatgctggtg ggcgagccgc 8880 tgcggactcc cattatcatt cgtgatgacg gcaaagcctt caccttgacc tggccagaga 8940 tcatcaacct ggcgcgctcg gcgttcgcta tcgatgacgc ggccgattga tttgtcttcc 9000 agaaatttta gacaatctgt tcaaaagtgc tttactcgat gatgtgactg agatatagtt 9060 acctcatcga aacgcgaaac actccaaaaa gaggattgcg acatgactag ctccaagtgg 9120 accatcggca gaaacgacac catcgaagtc gaggccgtaa acagccgcga agatttccgc 9180 tggaatggca aggttcgcgt catccactac agcgccggtc aaatcgtcaa catcatcgag 9240 ttctatcacc acgatctgga ctgggcgatc aagaatttcg gtatcaagct gaaggctatc 9300 tccaagggca tggaaatcct ccacacctgc tacttcggga agtatgtcaa atgatcgtcc 9360 aactcgactc ccaagaagag aaaatcatcg gcctgagaac tctgtccaag tatcgtcgcg 9420 ccggtggcaa gttcgcaccg gtggacggaa ctcagaccgg tccctggggt ccagtcgaca 9480 acgcgctttg ggcgaagctc gaagccgaag ccagggcaga atacatccgc aaacaggagc 9540 gtaaagcatg atcaagcaag acctgtacaa gcagatcgcc ttcgaggcga ttggctccgg 9600 catcaagatg ttcgtcaagc tttactgcaa cgacaccatc ctggaagtca tcggcgtcga 9660 ggaggcccac attgatggga cgactcggct gcgttacacc ggccacgccg atggtgtcga 9720 tgtccatttc ttcatcaatg aaatcgacat ggtgatggta tgagtggcca ttctatgttc 9780 gactttgaag tcgatttcaa tagcgccacc aatagcgcca ccatggagat cgatcccggc 9840 tcattctatg taggcttcgg gtttggtgcg actgctctgt cagtcctgat ttatgtagat 9900 ggagtatggg tgagcgaacg gacggcatgg attccagatc caaaagagat atcgccatga 9960 gcaagcgcaa aaacgatcaa ggcggctggg cgcagcccgg caatgctcgc aaagtccact 10020 tcttcgcggc ggacggccgc agtctgtgca agcgctggct gtatctcggc aagacttaca 10080 gcgagctgcc cgacctggaa atcacctgcg cgatctgcga gaagaagcgc cagagtcctt 10140 tcgaggaata ctgcgacacc attctctaac gttcaagcct tcaaaaaccg aggaaccgcc 10200 atgaaactct accatgcaaa agtcagccct ccatccttct atcgccacaa ccagaccgac 10260 gaagagcgga aagccttgga ggcggaatat gtcagcaagc tccacgttct cctggggaac 10320 ctggaaggcg taacaatcgg gaatcctggt gagcggaact gggagccgtc caactggagc 10380 aacgacgttc ccgtgatgtg taatgaaatc ggcctgggcc gtctgaccgc ttcagcctgg 10440 gatctggaca aggactatcc gtacaccatc atcaacctgg tccttctctg ggacgacgtt 10500 gacccggaag ccgctctgcg acccatgctg gagcgtctgg agctggccgc gagccggttg 10560 gccggtatgt cagtaagcta catcaaccaa ccggagatgg tgagtggaat cgagggttgg 10620 aactcgctca caggatctgc catccctggt ccgaatctcc agagcataaa tcgtctccta 10680 ctcaaggaag actgctgcac ggatgaactc cagtccgccc tggacgcagg atggcgcctt 10740 ctcgccgttt gtccgcagga agcgcgccgg cccgactaca tcctgggccg attcgattct 10800 gtcccgccga ccggaccgcg tggcgcggcc aggagcatcg attaaatgac catggtaggc 10860 ccggctggaa agcgctactg gcttcggtat gaaaccagat actgggagtg tcttgacgga 10920 caaaccctgc ggctggtctt cgtcatcaac ggtcgccggt atgaggtcaa tcgacgagtg 10980 aatgtagaca tcctgtccag tcggcgcagg ttcgaatctt tcggccgagt cctggcaagg 11040 atggaaatca gcctgtggtt cgcagtgtgc gagcaagaag ggccatggcg cggtagcgta 11100 gccataagcg ataccgcact ttggttccac ctgacgggag aattggtaca caaatgcttt 11160 actcggcggt gagaatcagg gcataatctc ttcaccggct gagaagccgg acccgaagtc 11220 caaaaaggaa tctcgaaatg tacagaactc cctcgtccaa attcacgttc atttgcaacg 11280 gcctcgccca gaatacagaa gtgacggtcc tgctccggac gcagaagccg gaagatgtat 11340 gggtggtgga cgaagcttca gttgcgaacc tgattcgcat ccatgaacgc agcaatccgc 11400 gccgtcgccg taccatcagc atcctcgacg tggatgcagt gtccatcctt cacaaacgtt 11460 aatccatcgg cgcggctgga ttggtcccgg ccgcgccatt catgcaggag tgtattatgg 11520 ccaaaatatt gatggcctgt gagttgctcg tcggcgacga aatactcact catgttgacg 11580 tcaacgatcc cgttcggcgt cgggccatag tcctgcgatc tggagctgcg ccgcacagca 11640 aagtaagcat cgaagtctcg gcactcatcg gcgctgactg ggtggacttc aagctcaagt 11700 tggccaggga ctatcctacc atctgcttac atgacatcga cccgatccgc cctcgcggcg 11760 ctgcccaata ggagaacaca atggcaaaag ttgtaagagt tgatgagttg aaaactggcg 11820 atgaaattct gattaagctc agggcggatt ccgcagccag gaacaaggca attgtccttt 11880 ctgtcgaatg ctggcgcgac gaaatcaccc tggagcttac ctgcccggcc ggcgactact 11940 gggaagactg gcgcggtaaa tatcgcgcat atgacaaagt cgttctgttg aagcgcgact 12000 aacaacaacc agcctctgcg actcggcaga ggctttctca ttggagggca gcttatgtcc 12060 gataaagaac aaagtggcca ttactgggtg acggtcagtc cgaccgatct gtccagcgcg 12120 tcggccgcgc agcgactctg cgaaacgatc cgtctgagca tgacgcgagg cgtcgcagcc 12180 tacagcaagt tctacggctc gaaaggtgag tgcctggtga cgcgagtcat tccgcaccag 12240 tgcgaactat tcgtcaatga cgagtcgggc acgaatcggc gtcgaacggc gatgatgatc 12300 gaatacgtcc gcttcaaagt tccggccggt atgtctctgg tcgaacacca aaagcaacct 12360 tactgagggc gcaccatgct atacatctgg gaagatcaag acatccacca caacatcgaa 12420 actctggctt tcgtcggcga gtccaggtcc aactacacaa tcatcggatt cgaattcggt 12480 gatctgttcg ccatcgccaa agagtccact ggtcagatcg tggtaagcct gctgactcgg 12540 caagggatgg cggaatggct taccatgaac ggccatattc ctgccgagat catcagccac 12600 ggacccggca accacaaaaa cccgtatgta tgggcggact ccatcatcct gaacaatctg 12660 ccgacccatc cgaacatgcg ctgcgttacc actccattca cgggcttcga tccagcagaa 12720 ccgggtggcg acaagactgc cataggtcaa gtcatcaagg acaaccgatc cgccgaaatg 12780 ttcggcgaca atccgtcgca gcggtcgcag cggtcctttg gcggcatagc gccgagtctt 12840 cctgatctgc ccgatcttcc ggagccgccc agggcgccga tggctcctcc aggcctaccg 12900 gttccgcccg cgcctcatgc gccaaaagcg cctccagctc cgcaggtaag caggcagtcg 12960 gaatcgctgg cgcttcggtc gggtgcgatc ccttccagcc cggcgcccgc atcggacaac 13020 gacaggcccg gcgatccgcc catcgagcct atcacagtcc cgactttctg acatcacccc 13080 aacgccaaca aacaccgcag cctgctctgc ggtgttttca catccgacaa ccgttcgtcg 13140 gctttgcgat caatctgatg aaataaatgt agacacgcag catcgaccta ggcataatct 13200 ctttcaacgg ggcgacaaac cgaagcccga acgaaatctt ccaaaacaga ggatcgcaaa 13260 atgaccaact ccatcaaaac cttcggcgac atccagaacg cagaaatgaa agaactggtc 13320 gccttctaca acgcccacaa cgccgatgcg actgtcaagc gcttctctga ccgcaagacc 13380 gctgagcgtc gctgcctcgc catcctgaac gctctgccgg ccgaggaaga ggccttccag 13440 gaagaggaaa ccccggccaa ggtttacaaa acccgcactt ccaagaagaa ggcagaagag 13500 aaggccgaag agaatctgaa gccggaagaa gaaatcaccg aagaggaagc gctggaagaa 13560 atccggaaaa tgcgcgaaga ggcgaagaac gcgccggaga aaaccaaaga gaccaaagac 13620 ctgtcagcag ccatcgccaa ctcctggaaa gacccggaag tcgcccgcaa gcgcaccgag 13680 cgtcatggcg tggcggtcac cgtgaaaggc aagcgcggcg agttcaaatc ctgcaacgca 13740 gccttcatcg agttcggttt gccttcctct aagtgcatcc gattccgcat gcagctgaaa 13800 gcgtccggca aattgacttt cgagcacgaa ggcgtcaaat acaacttcga aatcatcgaa 13860 gctggagaat aagaaaccca aaagaaagcc ccggattctg aactagagtc cgggggcttt 13920 gtcgcttctg atcgttattg gtcggcttcc tagaacagcc ctagaatcgt ttttcgtccc 13980 ttcccgctac cttcgcctta gttcggtccg attcgggcct agaacgatgt tattttatgt 14040 ctaaatgggg ttggcgcggt cttcctcggt cggttccgga gacggagacg ggaaatctcc 14100 ctcttcacct tccggcacat agccattggc ttcggccgca gcagcgacgg tcgcggtctg 14160 agcctcggct tctgatgcgt agaaatcggc caaaccgcga ccgatccggg tcttgcccga 14220 ctcgtccacg aacgtgattt cagccagaac gttcaattcc ttgatggccg acagacggct 14280 ggagtccttg acggtggggt cacgaaccat ttggaggagt tcgtggagcg ccgtctttgg 14340 attccacaaa tcggacgttt tggtcgcgtt caacttggcc ttgaactgct tgcgatagta 14400 cgggttggac tccatcgcga agatgcgggc ctgcgcggga ccgtccatat gctcctcgcc 14460 ccagatggcc cggaagaccc gccaggagct gtaaccttgg acgcgcaggt cgatgtacag 14520 gtcgaatcgc ttttggttga tcgccgcgaa atgcgggtct gcgaattcct gtggcgtgac 14580 tagatcgtcg gggctgtaga atttggtcat ttggtgctgc gtccctgagt tcgattctgg 14640 agtcgtcgcg gtggctcggt tggtggatgg ggcctggtgc tctgtcgcga cactgagtat 14700 ggcgcgattg tactatgggg ccagggatcg cgtctatggg ctgcttgtgg gtgggctgta 14760 ggtctgggtg ggtttgatga tgaatgagtg ttaggtggtg ttataggatg ttatacgggc 14820 gatccgctgg tgggtgagga tcgagtcggc ggtggcggga gacgatggtg gtgagtgttt 14880 ggattgagtg ttaaatcgaa tgttagaaat atgtccagct gagcgattct gtcgcgctcc 14940 caaatttccg gttccgttcg tcgagttttg gcacttgccg cttagtccgc cgtggtgttg 15000 ccgcgaccca tggattggaa gtccggaagt ttccggcgac cctgccgcga gctggctgga 15060 atcggaaact tgacgggata tgtacaagct tagtgccgcg aggctttcaa atactaaagt 15120 ttaccaaatt accaaattac tattaattta attaatttta aagataggta acgtccgtga 15180 tagatttttt ctattaggat tgtgcaatcg attttcgctg tagaatagtt ttaacccatg 15240 ctcgaaaaac cggaaattag gaaattggcc cgctaaccca cgcggcagta ggcttcccaa 15300 attaccgctc agaatcgcta tacagtaatt tgcggctagt tcccacggaa agtccacctc 15360 aaacacgcaa tttctcaaca tttcacgcaa aatccatcca ccatacacgc taaaccgata 15420 ccgaaaatct atcgactttc cattattcgc gctcgaaact ggtccaaatt actgtattca 15480 cttctaccaa tcccgcccaa cgccggaatc taatgtacgc cgcaccaaag aaaagaccgc 15540 ccgaaggcgg cctagtccaa gtacactcaa ccactacatc agaaatcctc gcccaaaatc 15600 ttggctcgct cggcccggac tgcccgaatc tttgccatgg cggcctcatc agtgatatcc 15660 gggtcgccct tcctcagcaa gtacacaagc gcatcattga acggcggcag cgtggtttgc 15720 atactattcg tccatccagg tgcaacctta tcgacgggca ggcaccaacc agccaggccg 15780 ttcttgttcg ggacgaaccc cagcgccttc aggtgcggag ttaagtggcg agaaatcggc 15840 ttcttcctgg cgagaatatc gaaccatttc agaatggtga cggtgtcagc cctccaccca 15900 ggattcttgg aattcttgcc cggcttgatc tcttcgaact cgcaacttat cagaacgttg 15960 atcagataca tgtcaatcgt atcatcacga accacgccac gcgcattctc catttccgaa 16020 atagagaagt tctgcacttc gcggttagct tccgacacca tattcaggta tccatcgacg 16080 ccatgctctt cgatccaggc gcggcactca gccatagcct gccagaactt gcggccgaag 16140 tctgtgaagt ccaccttgaa cggttcatta ccatcgcccg gcttaaccca gttcggcttt 16200 ccatcttcgt cgggaagttg tgccacgaac atcggataga atcgacggtt gccggagtcg 16260 tcccgctgga gtccatcgta tccgttgccg tccatgatgg tgatccattg tcgcttgatc 16320 gtttcgcccg gctcgaattt ttgatcgaat gtatccgaag atcgcaccag gaattctttg 16380 atgcgttcca tgtcgccctt tttgaagccg gacatttccc cgacgttcgc aataaccgag 16440 ttgccggtga tgttgcgcag gaacggcgtc tggtcgtgtc ggctcaggtc gagctgaact 16500 ggagctagat cgcgcccacc ggacagttcc ttacagatca gcaagccgaa atatgatttc 16560 cccgcatcct gcccaccaat caacgccaac gagatcggcg ccgaaattcc cggatagttg 16620 atgcggcagt acaggctcag ccagaaatac ttgctcacca tacggttgag ctcggtgtcg 16680 aacggcttga aaagatcgat cagcaacgtg ctaattcgct cttcgccgtc ccaatccggt 16740 atcttcttct caaacgtctc gatcaaagag ttgcggcgat atcgacgcgc ccaaacgcag 16800 caagtctcaa tcgtcttctt aatcgatgga tcgtccaagg ccgcagccgc gagggcgccc 16860 atcaggtcaa tggggtcgag ggtcttgttg ttgaacgcca cgcctcggtg gtccaccagc 16920 cggccgcgaa actcgtcgaa gtgcgggtgt gggacggttc cgtcgccctt acagaacaac 16980 gtatcataga ccgcgaggta gttgctgtct gacgtcgagc tgtatttcgt gatgaagtca 17040 tcgaacggcc ctttcaccac ccggctgacc ggaagatcga acgcctggtc gagcatcaac 17100 aaccgcgctc gcttcctcaa gtctggttca gcatacgcct cggcgtatct tgccgccttt 17160 tgcgcgcgat gcgtttcgtt cctcgcaatc gcatcatcgg ccgccttgct cgcggcggtc 17220 atcaaagggt ccattccagc atcttctatc tgcgtgagat caaactcact ggaccctgat 17280 tcgccatcat caaaaatatt atcttcgtcg ataatcatgt taggtttgcc gccttctgct 17340 ttacatgatc ggattcaaca ttgcctctac acattgaggc gaaagggacg gctattatct 17400 cctacctaaa ccggcatagc taataagttc cgtccccatc cgaaaatttc tgtaccgttc 17460 gtcgattaaa atacgtcaaa cgcaacgacg aaccagaacg tcaaagcaga aaggccgaag 17520 aagaagcaca gaagcgacgc gaggaagttt gcgacttgta ttttccatcc ctttaggcct 17580 tcgaagaaga tgataaggcc gaggaacagc aagccgatgg cggtaatcag gattccatga 17640 tcgttttgca tattgtctac tcctcaccga tatgacggcg gttgattctt tccaattgtt 17700 cgatgatata gggtagcacg acttcatccg tgaaggccgc ccaagtccgg cgatgctctt 17760 tgcggcaagt atcgtgcccg caaccgaaca catattcgtg ctcggcgcca ggtatcggtc 17820 cgcgaaagta tgctccgaaa ggatcgccgt tggtgtgctc gtcgccccat ggacagcgga 17880 tgcggtattt gccggacata ttctgctgga cctggccgcc tgccgcttcg cccatcttgt 17940 atttcgtgca gatgtgctcg gcatacttca gccatacttg gtcatacacc caatcgtcgc 18000 ggtttatctc caccttcttc atctgtggca tgatgatgcg gacgccaaag gccttggcga 18060 tctcttccgg cgagtagcgc ttggaatagt cggcgctgta caggcgcacg agttcgggct 18120 tgccgttttc gtcggcatat ttgaacttgc cgtctttccc gcgcttgtta ttgaagccga 18180 agggcattcg gccgtaacgg ctgacgtcct tgactgtgtt gtcgccgcct ttctttagca 18240 cctggtccac gaacgaatag agcagcgcct tgaactggag catgtgggac atcggctctt 18300 tgaagaaata ccagaactgg tagttgttcg gcgaagtctc cacaatcgcg gtcggctcta 18360 gtcgctcgcg gaactcgtcg cggtcgaagt cgcctttgga ccctttgccg gagccgatgt 18420 catcgaccat caacgccagg ccgtggccga aagaggcttc gccgcgccag taccgcatct 18480 ggcccgtctt cgggttgggc gtcttgatgg acgacgatat acaggcgtag gcgttggatc 18540 gt; ggccgttctc gtcggtctgg actgtggctt cttcagcgta gccgaccatc acccgttcgt 18660 cgtccggaat ccctctgccg agttctcgca ggaattcttc ggcctgagcc agtcttattt 18720 cgtgaggctt catgcaagtc gctccggtct tcctttgcgg cgaggtactc caacgaactg 18780 tcgcgcagca ctcgcctttc tggcggagtt taggccatct tcatggattc gactccaggc 18840 ttccatgatc ttgtgctgtc tcgccttttc gagcgccggg ggaatcttcg catcgtcgat 18900 gccgcgcacc cacatgaaca tcaggaacgt cgccaggtcc aggaggttgt tctcatttcc 18960 cttcagcgca tgttcggcga atccgttgat cagaacgtct tcgtcgcagt cgatccagcc 19020 gcctcggcct ttatcgcggg agcgctgtag tttctggcgg atcgctgctg cgaacatgga 19080 cacggcgcac tcgtcctgcg cttctggctt cgcctttcga agaatgcgaa tgtcgagatc 19140 ggtcatggcg atggctccat ctacttccga aggtttctgc tgttccatta catgaactcc 19200 ttgcttggca cttaccgctc gcacccgcag cgggcaggat gggcctgtgg ttgctggcac 19260 ggctgaggat gcgcggccgg atcgatgggt gagggcgcta cgtcgagcat ttgccggtaa 19320 atctcgccga tgctgtttgc cgcgtcataa cgcagggact gaccgacaga ggtcatctgt 19380 gatgtcgggt ccatcggtac gagcttccac ccctccggca cgctgggttg agccttggcg 19440 accgctagcg cctcgttgag ccggaaccct tcgtgcaccc agtccgtcaa cttcccttcc 19500 agctccgcga ccctggccaa ggcggcgtcg agtcgttttg cattctcgtc gcgctcgtac 19560 atcatcttca tacacctgtc gaagctgcca gagggatcgc cttttgattc tcgcaggcgc 19620 tcgacttcgg ccaaggcggc gtcgcgttcc actttataac gacaataagg atggccgtat 19680 tcatcgccga ctacgccgtc acaatagctc gcggccagct cgctcccgcg cttttcggat 19740 tcgtccaact tcttctccag cagcgaaatc gtctccagag catcatagag tttgttggcg 19800 tcggtcttct caaactcagg gatgcttggg cgattttcgc tttgttcttt ttccatatta 19860 ttccccagca ctcccaggat tcgccttctg ccggcatcag ttatgttcca gcaaggttgg 19920 cgaccgaaca tatatccagc cacggaatcc ttccatgata gctcgacaag cccctttcgt 19980 ctcaaagcct taagagtcaa attcgttggc gatctgtgaa ctggatgctc aggatgcctg 20040 tacatttcca gtagaacggc atgctgccga ggactcagct ttggactcag ctttcccaaa 20100 tcttccatat cattcacctc aattacagat ggcgatgttg agaactttat cgcgcccggc 20160 cgcgaacttc tccaggaagt ccaccaggtc attcaggatg gtccccgctc gacctagctt 20220 gtggccgatc aggagctgcg cgactcggtg tccgacgaat ttccccgaag gaattttcgg 20280 ccatgtttcg ccgatgcttt tgagtactgc atcagtgtag tctttgtccg cgccgacttt 20340 gtggtgatcg aggatcgtgc gatcacgaac gtatcgattg atgatccgcc gcaggaactc 20400 gtcttcagtc ccggccaggg cgccgcactc gcggagctgg cgcaggagac gccatccaag 20460 gttccgctcc cacttttcag agaactcttc ggcttcggcg aatgacgctc gcatgatgtg 20520 atcgaccggg atgatgacgg cgccgccttc tttcgttccg gcttccatga ccgcccattc 20580 gccatgctcg cggtgctcga tgaagccgat cagcatgccg atgaaagctc catcttccgg 20640 aactccggtc acgcgaacta cagaatggcg cgggaaggct ttcgatccat aaaggctgga 20700 ctgtgaattg acccatccgg ccttggccaa gtcggacgct tcggcgtgga tcagctcgcg 20760 acgaatgcga actgccagcg ccgggtccag ctcgcggctg cggcgcagga aaccgggctt 20820 caggttcggg tcgcgggtct tgtcgacatt gggattcgga ttaccgaccg ggagttggtc 20880 gcgggaaatc ttgcattctt gcatttagtg tatcctctgt tttggagggc agtacaggcg 20940 gcggcgctag tatcggccac tttcctgccg aagtaaagtt ggattaaatt cgctcgcttt 21000 ggcgagtcag ctgatagtat actcttcctg cgcagaggta aagcataact gtacgttata 21060 aaggaacatt cgatggcgga acatattttt actcacgaag gcacggtggt gttcgagggg 21120 cgatcccgaa cggtcaagct ccggcgcggc aaccaccact gggtagactt cgatagacat 21180 cgctatagcc cacaggacgg ccgcgccgct tcccaggcta ttaagggtgc ggtcctggtc 21240 ctttcgaccg tccgctggct ccctggggcc aaagaggccg cagagcaggc gaaggctttc 21300 ccgtataaag gaagggtcca cgcgcttgga gccgcttggc attatgttct gctgcggcgc 21360 acgaagaact tctatgtcga tccgcaaggc cgcaagtatc gtcgtgacac tggatggtct 21420 gtggacggcg tgcttaaact gagcctcgat tcaattaaac ctagcgttgg agaacgcaaa 21480 tatgtcagca tctaacttca ccgtcgatca gatcgaagag cgattcggct ttcgaccaaa 21540 cagtcagcag atcgacgcga tcaattccgt tgtggactgg tatcgcggtt ggtgtgatcg 21600 agcgcaccgc cgccaggtct atcgactcgc tggtttcgcc ggaactggta agacttccat 21660 cgcgaagatc atcgccgaac tttgctgctc gatggactgg acagtcttcg tcgcgccaac 21720 cgggaaagca gcagcgcggc ttcgcgagaa gggttgcacc aatgcccgga ccctccacag 21780 cttcatctat cggccgattg gtgaagatga agacggcgaa atcatgtttg ccaacaaaga 21840 ctcgctcgac gagaagccga agttggtcgt gctcgacgag tcgtccatga tcggcgagtg 21900 ggatgaagag cgcttgctgt cgcaccggat tccggttctg gagattggtg actttggcca 21960 agttcctcct gtgcgcggcg tccagatttt ccatgagaac agctgtgaca ccatcatgac 22020 cgaaatcgag cgcaacgccg gcaatatcgt tcgggcgtcg atgttcgtcc gccagggcaa 22080 gcgcctaccc tgccgcgagt atgacgacat cctggtacgg gccggattcg acatgtcgga 22140 cgacgaaatg cggacgttct tggacgatga tggcgtgatc ctttgcgcct acaacaatac 22200 tcgccgccgt ttgaacgcca gggcgcgccg catcctcggc tacaagggtg tacaaccgga 22260 aatcggcgag aagctggtgt gcaccgggaa ccagcacgaa tatggcatca tgaacggcga 22320 gcaagcaatt ctgctggact tcaagccggt ccccgaaggc caagaagatg atgacgagcc 22380 ggatgaaatg ctgtttgcca aagttcgcat tatcggcacg aactatgagc gctgggtgaa 22440 gttcaatcct cttagctttt cggttgagga agatgtgcgg ctggaggcac agaaggccat 22500 tggcggattc gacttcggct gggcgatgac gttccacaag tcgcagggat cggaatggaa 22560 gcgggtcgca atgttggaag aaaacttgcc ttcaattcct tacagccagt tgatgtatac 22620 tggcataact cgcgcaattg aatacttgtt gtttttgcgt aagagttaaa aacttcgcta 22680 acataaataa gttccctgga gtctggactt tcccgaaaga aaaatattta gagaagttca 22740 ggcgaaaggt attcccttct tcaattagtt tagagataat cctctcacag gccaataagc 22800 catcctttca aacattcccg gagtaagaac atggaccaga acgaacagac ccaaggcgaa 22860 gagctgacca aggaacaagc agccgccctg cgcaaggccg agaaggccgc cgagcgtcaa 22920 cgtaaagagc gcgagcgcgc cgagaaggcc gaggccaagg ccaaggaagc cgaacagaag 22980 aaagccgagc gcgaagagaa gcgcaaggcc gagcgtgaga agaaggaagc agagcgcgcc 23040 gagaaggcga aggaaaaggc cgccgccaag gaggccgagc gtgctgaaaa ggccaaggcg 23100 aaggaagccg agcaggccga gaaggcgaag gccaaggaag ccgagcgcga gcagaagaag 23160 gccgagaagg aagccgagcg agccaaaaag gccgaagaga agaaggccgc ccaggaagct 23220 cgaaagtcg ctcgtgaaga agagcgcaag cgcctggccg agcagaagaa ggccgagcgc 23280 gaagccgaga agcagcgccg caaggaagag caggaagagc gccgtgcgaa ggccgaagcc 23340 cgtcgtgaag aactgaagtc caacggctcg cgtcgccctc gcgccaccca cttcatcccg 23400 accggcgacg gccatggcac cccgcaggcc atttcgattc gcggcaaggt gtttgcctac 23460 atcaacgaga actgcgccgt cggtgagccg gtagaaatcg aagcttttgg cgagaaagtg 23520 gcacacctgc tgtatggagc ctcggttcgc agctatctga gcaagctgga agtcatgggc 23580 tgggtcgatc tggttgccat cgcttcgaag gaagacgaag ctggccaggg cgatgacgag 23640 aaggccggtg atgaaggcca ggagcacgac ggtgaagatc agggcgccga cggttccgat 23700 ggtgaagaag agtaagccgc cgctcttctg agactgaatc gtctagctct tcaagggact 23760 catgaaaatg ggtccctttt tatcctctca agttttgtac actcagaagg aacacaccat 23820 gattcctgat cagaaagtca tcatcgtagg tgctggactc gccggactga tcgccgcgca 23880 tcgctttcct caagcccaaa tcatcgacgc ggcgacgccg gagaacaagg agcgtcacaa 23940 cgcactcttg cgattccgct cgccagtaat tggccaactc accggtatcc cgttccgcga 24000 agtcactgta cacaaagcta tctacatcga cggcgagttc atctcccagc cgcgcatcga 24060 ccactgcaac atgtactcca ggaaagtaac gggcggcctg tcggatcggt ccatctggaa 24120 tatggcgacc gaaaagcggt ggatcgctcc ggccgactac tatgagcagc tggtcgctaa 24180 gctggcgaat cgcatcagct ggggcaggcc tttcgacgcc tctttcttcc agttccttcg 24240 ccggcaagat gatcacgtta atatcatcag cacagcacca ttccgcgcca atctggctgc 24300 ggcaggactg gacctgggta tcgacccgtc attcggcgaa ggcacctcca tcgtcgtaag 24360 tcggtacaag ctttccattc cttgtgatgt cttccaaacg gtgtacttcc ccggtccaga 24420 agtcggaacg tttcgagcgt caatcaccgg tgatacccta atcgtcgaat ccattactaa 24480 gggagtggtg gagactgctg cgggcgaaat caaaaccatc gaatgggaca gcgcctggga 24540 cctggatgac gtctgctcgg ccttcggcat caggaagaag aatctcattc aggacggcga 24600 gccgaccatc cagaccaagg gtaaaatcat tccgctcggt cgcgatgagc gcgaatccat 24660 gatttggaat ctcacccatg aagccggcat cttctcgcta ggtcggttcg cgacttggcg 24720 aaacgtcctt ctggacgatc tggtttctga catggacgtc atcgagcgcc tgatgacttc 24780 ttcgtcttat cagaaggcca agcagatgtt cgtgaagtaa tttacaaaag tgctttactt 24840 ctggatcagg tgggcgtaat attccctcat cgaaacgcga aacccttcaa ccaaaaggaa 24900 tcgacaaatg gcccgcgaag taaccttctc caccgacaag aaccacacca aaacctacgc 24960 caccaaggcc aatctcgaac gcgctatcgc caaggccgaa tggctcggtg aaggcgcccg 25020 ctacttcata catatgaccg aggacggccg cctgactcct gtgttccttc tgaatagcct 25080 tcctgcaggg gccggtgcgg tttggtgcgc tcagcacggc tggaacgtgg taggttaatg 25140 gccgtcgatc ctcgcgaggc agcgctcaag cgggcgctgc tggctttctt cagggacacc 25200 gatgcccttg gcggcgggag tctcaccata acggcccgga tcgtcgggcc agagggtgac 25260 aggaagtttc gcgccagtta tttcctgaat ggcgagaagc tgagcctgtc agatataatc 25320 gctaaagtgg aggccgaaga tgggccggat cgttaatatc aaagcagtca tttctcgcac 25380 gaccgagcgc gattcgatgg ggtcgccgta catccatgag tcttaccgca ctttctcttt 25440 ctccgcttcc accacactgg tcgcggccat cgactgggtg aaaggccagt gcccggaaat 25500 cgttgacatg ctcatctacg agccggaaac cgtagctgct cagcaggagc gctattaatt 25560 tacgcaccag atcatcctga agaggttcct atgtccttcc tcgaactcga aatgcaagcc 25620 gaccagcagc cgaagaccgc gccgtctttc gttctggtag gcatcctgta tcaaaccggc 25680 gctgaactgg acgataagcc tttcacttcg ttcaacctgt cgttcggcag tcgagaagag 25740 gccgagcgcg cccgcgataa gattcgtgag cactacctcg atcgtcgaga tatccgcgcc 25800 gaaatcatcc gctgctactg aggtcatcat gtcgattgaa cttgtgtacc gaacctctga 25860 tggaaccgtt ttctcatccg ttcaggaggc tgaagagtat gagtcgcgtc tggaggcctg 25920 cgaactgctc aaggaagaga tagagcagta tggccttcgt aaagagcaag cccaaggcct 25980 ggccctggct ctaaccaaaa aattccactt cacgccaatt ccggaagatt tctgatgaaa 26040 atttctctga tcagttacac ccagaacgcc tgggaacttc tcctggggac gaaatccact 26100 cgcatgcgcg gccaagaccc ggcgaccatg accgaggccg aaaagcttga ccactggaag 26160 tacatgctgg acaccatccg ctcgccgttc gagttcgtgg acttcatttt ccagatcgag 26220 ggtgtcagca agaacttcac ccatcaactc gttcggactc gtaccggggc ttaccaacag 26280 gaaaccagtc gcgctctgga aatcagcgcc gtcgttcagc cggaagcctt ccgctgggaa 26340 ttcgacgaac cggttacggt aaatggcgag cctgacccga cctaccatgt ccgcgaagag 26400 ctgaaccgtc tgtggcatga cgccattgcc gacgcgcaaa ccagctacca gaagcttctg 26460 gggccggcg cgtcgctcca ggacgctcgt gccatcatcc cttccaacat ggaaacgaag 26520 atcgcggcca agttcaatct gcggactctc agcgacatgg cgaaggttcg cctgtgcgtt 26580 cggacccagg gtgaatatca ggaagtattc cgcgaaatgc gccggctggt tctggaagtc 26640 tatcctatgt tcgacagcct gctccagccg cactgcgtcg ccaccggctc ctgcgccttc 26700 ccgcgctatg ggtcgaaggt gatgaatgaa gaggaaatcc agcagaaatc ctatgaccgg 26760 ttcatggccg ctctggagac aaagccaggt cagattcctg tgattgatgt tccgttggaa 26820 cctatctacc agtgcaagtt ctatcgcccc tggatggatc gctcggccga gcaggaagaa 26880 ctgcgccgcg atttctgggg atcggaaaaa caagaggcca accctgtggc cgtcaatggg 26940 aagtccatgt aacatgaaga tcattgtcga gaaagttgga gacatcgcac aagtcgaagt 27000 gaccaacggc agcgaatcca ttcgcatcac gatgaacgtg caatcgttcg atttcatcca 27060 gaatggcgaa gttttccgcc tcacttctga tgggacgttc atcgataaaa ccgtcaccca 27120 gaaagcaacc agtaaggaaa tctgaatatg gaacgcaaac caaagaatgg catcatcatc 27180 ttcgacctgg acggctgcgt attcgacgat agccaccgca agagcttcgc cttggaacgg 27240 caatgggacg agtatcattc tcgtctcgac aaggacactc tcaacccgca cgctgtaggt 27300 cgcatcagga atgccatcga cgccgacctc atgattttct tcgtcaccgg ccgaaccgac 27360 aaccactttt tccagaccag ggccaagctc caccgcgaac tcggcatcgc cgaacatcgc 27420 gagtatgaac tcatcatgcg gccgtatggt aacaccgagc cggcgcctca gttcaagcgg 27480 gcagtcgcgc tcgacatcct gaagaaaatc gaaggcgtca ccaagatcgt cgcggcgttc 27540 gatgatcgcc aggacatcat cgatgcctac aatagcctgg ggatcgactc ctacatcctg 27600 aacctggaag gttgcgctgc gccgttcttc gccgtcgcgg ccgatagcga ccccgatagc 27660 gcgcccaacg acatggcagg cgagccgttc ccggccgccc cgaactccgc ccctaccctc 27720 gacgaggcgt ttgcgaaagc cccgtctccg ctcgcggaaa cggctcagtc cgaagacccg 27780 accgaagacg ccgcgccgtt cgccatggaa tccgtctggc cgggcgaaga tgattcccat 27840 ccagatgatt tcgcggaaga tgttctcaac aatctgtacg ccgcagcaga agtcttccgc 27900 gcccgccaga gcacctatgg tcgcaatgat ctgatgtacg gaaagatcat ggaaatcctc 27960 ttcccgaacg gcctggtggc gaagaccgcc gatgatcatc gactcgccct gttcgtgatg 28020 cacatggtgg gtaaactcac tcgcctggcg aatagcgggt tcaaggatgc cgattcggcc 28080 ttggactcga tcaactattc ggcgtttgtt cacgccacca tgcgctccgg ccgcatcacg 28140 ccaaaagacg gacagaaggc gtaaatcttc agccgtcgcg gtatactcct caggccggtc 28200 gcgaaagcag ccggcctttc gacataagag ggaacaaaca tgatattcgc tgtatgggat 28260 actgagacca caggactccc gttccaccaa agggtgagtc tgagaaagca gccgagaatc 28320 atcgaattcg ccggcgtgat aactgatggc gaaaagattt tggatgaagt agagttcatc 28380 tgcaatcctg gaatcgtcat cgaggaaatc atcaccaaga tcaccgggtt gaagaacgaa 28440 gacctgatca agcacccatc tttcctcgat cagcgccaaa aagttcgcga cttctttgcc 28500 agagccgacg cgaatattgc ccacaacctg ccattcgata agttcatgct tacctgcgat 28560 ttggctcgcg gaaagctcgg cctggaagaa gtcaatttcc catcactcga tatctgtact 28620 gtggaagagt cggcgccgtt gttcggccac cgcatgcggt tgcaacatct ttatgagcac 28680 tactgcggcc catatgtaca gaaacaccgg gcgctcgacg acgtgcggct gctccacgaa 28740 gtctgcaagc gcatgggagt gtatcgggcg tatcaagcaa tggaggccgc ataatgtctt 28800 tccctcaact ccgcgttcgc tccggttact cctatggcgc cgcatatggc cgattcccgg 28860 agatcatcga gcgcgccaaa gagatcgaat ccccattcgt cgccatcgtc gatgatggaa 28920 catggggtca cgtccgttgg gagcaggccg ctgtcaaagc agaactgcct cgcggattcg 28980 gcatggaaat accgatcaaa tgcgccgacg acggcgaaaa agagctgaag ctcaaagcct 29040 gggtgctcgc caaggacacc aagaagttct accgcttgac ttccaagtcg gtccagaatc 29100 aagggttgac tccgcaagaa ttccaggaag ctgacggtgt catcaaattc gctggcgagg 29160 cgtatgccca tttggatctg gccggaatcg actacattga catcaatccc gcgtcgatgg 29220 tcgccgcgca cggcgctatg gagacggcca gggcattcgg aaagccggtg gtaattacct 29280 cttacaacga catgccgtcc atcgaccatg ctgatttcgc gtcggcctgg aaggtgcggg 29340 aatcggtcgg ccttcgccac atcgccaccg aagaggagct gtggagccgt ttacgccaca 29400 tcatgactcg cgaagagttc gattccgcca tcgccaatac tcgtgcggta gtcgagcagt 29460 tggcggatgt gaaactggcg aaggcgccga tgatccatct ggatggtgat atcgtcgctc 29520 tggctcgcga ggggcaagcc taccgcctca gtcgcggcca catcaaggaa tggacccagg 29580 agtatgagga tcgattccaa gaagagatca agcagattca gctgaaagat ttcgacagct 29640 acttcctggt cgtggcagat ttggtcgcgt ttgccaagaa gcacatgctg gtcggtccag 29700 ctcgcggctc ttctgccggc tctttggtct gctatctcct tggaatcaca gaggttgacc 29760 cgctcccgca tcgcctcctc ttccagcgct ttatcgacat ttcccgttcc gatcttcccg 29820 atatagatat cgacttcgcc gatacccatc gctatctagt gttcgaatac ctccagcaga 29880 agtatggcac ttggaacgtg gtgaagttgg gtaacattaa cacgctcaag gccgcatcgg 29940 ttatcgctca cgtcggaaag cgcttcggca tccccttcca cgataccgac aacatcaaaa 30000 actcgatcat tgaatatacg tcggcggacg aacgatatgg aaaaggattg gaggacactt 30060 tcgaaaaaac tcaacccggc cgcgacttcc gcgaaaagta tgagatcgcg tccgcctgca 30120 tgggcgacct cgaaattcac ccatcccact ctggcgtcca cgcggcaggc atcctggtct 30180 gcaacgatga agtcatcaac ttctgtacgg taacttctga aggcgtcgcg cagctcgaca 30240 agcccgattc ggaatatctg aatcttctca aaattgatgc gctcggcctt cgaactctgg 30300 gagtcatcca ggacgcgaac tgcgtgaccg cgcaagagtt gtacgacttg cctttgaacg 30360 acaaggcggt tctggacgtc ctcaatgaag acaaaatgtc cggcatcttc cagttcgaag 30420 ggcaggccgt tcgctcggta gcgaacgcga tcaacatcac cgcgttcgag aacatcgacc 30480 acatcacggc gctcgcccgt ccgggtccgt tgtcttctgg tatggcaacc aagtacatcg 30540 agcgcgtggc cggccgcgag cctgtgacct ataccattcc gcaggtcgag caatatctgt 30600 cagggacgta cggcgtcttc ctatatcagg aacagatcat gtccatcgtc aaggacatcg 30660 gacagttcga ctgggagcag acatcggcaa tccggaaagc catgtctgcg cgaaagggtg 30720 aagagttctt caacaagcgc cgggaattgt tcatcgaggg tgccaagacc ataggcgtcg 30780 ccccggacga tgctcaccgt gtgtggcagg aaatggtgac attcggcgcc tggggattca 30840 accgctccca ctcggtcagc tacgccgtgg tgacgtactg gacctgctac atgaagcggt 30900 atcatcgcct ggaatacgcg gccgcgtgtc ttcgggcggc gaaagacgac cagcaaactg 30960 tgtcaatcct tcgcgaattg gccaaggaag gcgtagaata tacggccctg gacccggagc 31020 attccgaact taactgggta gtggcggacg ggcgcctgat cggcggcatc atgaacgcca 31080 aaggcttcgg cccggcgaaa gccgagaggt tcctgcgcct tcgcgaggaa gttaaggccg 31140 caaggatcgc cctggccaat tgcccgatat cggcakhga tgttgaggac aaggctgctg 31200 atgtagcagc gctggaagcc cagattcttt cggcgaaaat cagccaagac aaagaactgg 31260 aaaaactgtt gaaggccgat ctgaaggagt taaaggcaga tcttagggag ctgaaagctc 31320 aatataaaga gctggccgga acccacctga agacgcttca ggattgggag aaagtcgccg 31380 cgagtctgtc gaattctgaa gttcaattcg cagatttgaa cgaagctcac acgctctggg 31440 gtcatgctta tgacaatccg gagctggttg gagtaacttc cggaaacccc atccagaaca 31500 ttcgggatat ccgcgatgga gacgatggcc tggtcattgt caagatggtg aaaaaagttc 31560 tgtctgatga gaacgaaccg attcgccaga agaagagggc agatcaaggg aaaaacccgg 31620 tgtacaaggg ccagtcgcag tttctcgaca tcatgtgtgt tgacgactcg gtcgatcagc 31680 cgatacgttt cagaattagg cctgaaaaat atctgcaata cggaaagcag attgccgaag 31740 ggacgccgac cggctcttgg ttcctgatca aaggctggaa gctcagcgga atcgatatgt 31800 tcatcgtgaa ggccgtcaag aggattttga ccgaacgcga aaaagcaaag ctggcagcgc 31860 aagcagagaa agtttccaaa gagggcgaag gcgatgaatg atcgcgaaac gaaagcggcg 31920 aatacgttta agcaacgctc gctcggccga atcctgatcg actttctgga gacgcggcgg 31980 tctggtatgt ccgattcgat ttgcctgaat cgtcgaggtg tccagttctg ggtcgagttc 32040 aaggcgttgg aggagtggcc gaaacgcgcc tccacctgcc caatggccag atgtttcgag 32100 cctgggcaaa tccctttcct tcgggaacgg atcggctggg gcggccgggg cttcgtcctg 32160 gccaagatcg ggaccgattg gctgctgctg aatcccatgc tcgatttgtt cgagcttaac 32220 agccgcgact tggtggaagt tgcgagctat gcagaaggac tggataacat tgttcagttc 32280 ctcgccgatt tggagaacaa atgaaagcca aaacatatcc cgtcaagggc atgaagaccg 32340 aggccatgca gcaccagttc aatgccctgg ccgcgtccct gaacaaacgg aatttcgcat 32400 acctgatgga gcagggcacc gggaagactt ggacgacttt ggccgatgcc gttcgcctct 32460 tcctacaggg gcgcgtggac gcgctgctca tcgtcgcccc caaaggcgtc cacaccaact 32520 ggattctgcg cgagattccc acccacgtcg cgatcaagac tttgagcgtg gattggcgcg 32580 gccgaccgac ttccaaaaag gccagggcgc gcttggatcg tctgtatgcc gagacgttcg 32640 cagatgaaaa agttcttcgc gtcttcgcca tcaacgttga cgccatcaat caccaggctg 32700 gctatgatga agtcttgcga ttccttgaaa ctttcaaggt ttgcgcaatt gttgacgagt 32760 ccacgaggat caaaaacccg caagccaagc gtgcgaaaaa gatcgtaaag ctgggtgaga 32820 aggccgtggc ccgtcgcatc ctttccggaa ctcctctaac gcgggcgcct accgatttgt 32880 tcatgcagtt ccaattcttg cgcgatggaa ttcttggaac gaaatcctat cgggcgttcg 32940 tggccgaatt ttccgttttg gttcccagtg acgatcctcg aatgatcgct atcatgcgca 33000 agctggaagg gaagcaaacc atgccgccgc aactggtcga aaaagacgag cgtgggcgcc 33060 cggtattccg gaacctggac aagctgcggt ccctgatcga gccgcacagt ttccgggtca 33120 cgaagaagga agcactccca ttcctgccgg acaaggtgta caagcgcata tacttcgaaa 33180 tgtcgccgga gcaacgaaaa gtttaccagc gcgtggaaga agactaccac ttcgttctca 33240 agaacgaaga cttcatgctg gacgtatctt tcgatgctgc ggcagcgcgt tcgaagctca 33300 agcaagttgc atccggctat atcaacgtct atggcgagcc ggtgatcctg ccgcccgaag 33360 acaacccgcg attcgccgtg tttactgatc ttctggaggg tctgctggag gaagacccgg 33420 agcgctccat catcatctgg gccatgcgca ttcaggaaat cgaccagatc aaggcgtatc 33480 tggaggccca aggaatttcg tttggcacat actacggcga gaccaaagag gccgagcggg 33540 aaaaattgat cgacgatttc caggccaagc gcgtccaggt gttcctgggc aacccggccg 33600 cagcagggat cgggatcacg ctcaccgccg cagacgtggc catttactac acgaccgacg 33660 aagacaacga gctgcggatg cagtccgaag accgaaatca ccgaatcggc accgtcaact 33720 cggttttgta cttcgacctg atctgtctgg attccatcga cgagaaaatc caggtcagct 33780 tggagtggaa gcgcaacctg gcaagttatg tcgttgatgg agtgtttgag gctgacgtta 33840 gcactcgcga cgaaatttaa tatgtaaatc agtagccgta tcaaggaaga tgcggcataa 33900 tatctactca atacttagtt caagtaaggg aacatcacta agttggaggc ggacatgaaa 33960 gagcaagagc ttgaaatccc ggaatacctg aaagagaacg caccgggcga aatcgactat 34020 tttggcgtca tggatgaaat ggcggtcgaa gccaccgaca tcggccatcg actgctgaac 34080 ctggtggaca aggcttcgca gctggacgtc gaaatcctcg atcttcaaaa ggcgctggcc 34140 gaaaaggaag aggagctgaa aaccctcaag cgcaacacca ttccggagct gttggaggag 34200 cttggtcaaa agaccactac tctggcggac ggtcgcacgg tcaaagtcga gccgaaggcc 34260 atcatttccg tcaaggaaga gaacaaatcg aagttctgga agtggctgga agacaccgac 34320 aacgacggca tcatcaagac caaggttctg gccgagttcg gtcgcggcga aatggaagat 34380 gcgaagaagg cggccgaggc catcatcgaa gccggctatg acgccaccat caaccgcgat 34440 gtccattacc agaccctcca ggcgttcggc cgcgagtatc tggagaaggg cgaagagctg 34500 ccagatttca tcggcgtgca cgaatacaaa gaggccaaga tcacgaaacc gaaggtgaaa 34560 aagagcaaat cttaatatgt aatttgcttt acttagttgc aacttccgtt attataaacc 34620 cacagttagc gataactgaa attcgacaaa caaggagcct aacatggctg gtaagaaaac 34680 cgaaacttcc gaagcaactg aagaaaccaa ggccgttgca gtggccaacg gcggcgccgt 34740 cgcgactact gacgttcccg acttcatgga cctgtacgcg tatgacggcg ccggtttcga 34800 aggggctgac gcagattcct atgccattcc cttcatccaa gtgctgcaaa agatgtcgcc 34860 gcaggtcgat gaagacgatc cgaagtacat cgagggcgcg aaggccggca tgttcctgaa 34920 taccgtcacc ggcaagattt acgacggcaa gaccggtctg ctgatcatcc cggccgcgta 34980 tcgtcgcgag ttcatccgct gggctggtcg cgaggccgag ggcggtttca aagggtccat 35040 cagcgtcgaa gacttcaagg aaatgatgaa agaccctacc aaggtcaagg aagtcgaagg 35100 acgcctgtac gcgccgaacg aagacggctc ggtcagcgac aagaagtctg actacttcgc 35160 cgacacccgt ggtcattacg tcatcgtcat cgatccggac accggcgatt tcggccaggc 35220 tctgatctcc ctgtcgtctt cgcagatcaa ggcctcgaaa aagctcatga ccgcgctgtc 35280 ccagaaaaag gttcagaccc cgcagggcct gcgcaccccg ccgactttcg ccaacctggt 35340 ccgcatgacc accgtaggca tgtcgaacga caagggcagc tggtccggcg tccagttcga 35400 gctggaaggc ctggtgaaga acccggatca cttcaaggct gcggccgacc tgtacaagtc 35460 gttcgtcggc ggcgaggtga aggtggacta cagcaagcag gaacagcctc gcagtgacgc 35520 cggtggcgtc ggcgatgcga ccgaagccga agagttctaa aaatcaccgg ccggagaaag 35580 gcgctgtaat ggcgcctttc ttctgaggag tcgaaaatgg actggaagga cataggtagt 35640 aagatcggcg cggctgcccc ggctcttggg tcgctcctgg gtgggcctgc aggcgccgcc 35700 gtgggcgcta tcgtcgcgac ggcgctgggg tcgaaggccg acccagcctc ggtcgcgagc 35760 gctctagacg cgaatccgga agctctagcg cgcctcgccg aactccagag cgccgagcgc 35820 gttcgtctcc aggagcttgc gattcaagcc gaacaaaacc gccttcagtc tgagcagaac 35880 cagctccaag ccgagcttag ccagttcgcc gcagaggctg ccgacaggga ttcggcgagg 35940 aggcttgccg cgcagcagaa cgatttcgtt cgcccgtcga ttacattcgc tcttctgaca 36000 ggctccatcc tcatcatcat cgcaatcttc accttcggcc gcgaggctct gatggacccg 36060 acatcctcgg tcgccatcgg caccatcatc ggctattggt tcgccgaact gaagtcggta 36120 atggcattct acttcggcac caccaaggat ggatcgcgcc agagcacggc gtccatcatc 36180 aacgcagtaa aatcccaaat acagaaggaa tcgaaagaat gaacatcgaa caaatcatga 36240 gtcgcgaact tcacgacctg gttgtcaaat ggggcgccga ccggaacctg atcaaaggct 36300 cttcggccaa agatcaattc ctgaagttgg tcgaagagtt cgcggaagtt tgcgaagcct 36360 gggtccagaa caacccggtc gaggtgaaag acggcatcgg cgacgtaatg gtggttgcca 36420 cgatcatggc cgcgcaactc ggcgaaaatc tgttcgatca tctgtcggcc ttcatcgaga 36480 ctggcgaagc ccatcccacc tacggcgacg atttgcagcg cctcggacat cttgccggcg 36540 cgctggcacg cggaaatcag ggatttgcca tcaagagcct ggtttcggcc gtcatgactc 36600 tgttcgacgt gacggaagag cacgacacca ccatgctcga ctgctacgct gcggcctacg 36660 acaccatcaa ggatcgcaaa ggcgtcatgt acgacggcgt gttcatcaag gagtcggacg 36720 agcgctatgc gtcgatcatg gccgaactga accacgccaa cgaaaccatc tgagccggct 36780 taccgccatt tagcccggtt cgccgggctt cttttctgga gaactgtatg aaacccatgc 36840 tcgcatcgaa ttttgacccg aagctgctgg aaggccaact gccgatgtat ttctcgccga 36900 agatcgatgg atttcgctgc ttcgtattcg aaggcgaggc gctgactcgt caactcaagc 36960 ggcagaacaa tcaatcgatc tacgaatacc tcagcgataa actgttcaac ggcctggacg 37020 gcgagctggt ctgcggcgac atcagcgacc cgaaagtttt ccagaagtcg tccggcgatc 37080 ttcgccgcca cagcggtgag ccggactggt ctttccatgt gttcgatgat ttcaccgatc 37140 ctcgcgcacc gaccgaagat cgcctagcca gggcggccga gcgcgtgaac ttccttcgtc 37200 actgcctcgg ctatgagagg attcacctgg tcgagcagga actggtgact tccatcgaac 37260 agttcagcga agtcgagcgc cgccacacaa tgctgggatt cgaaggttcc atgggcaagc 37320 gcgctgatgg gctgtacaag ttcggtcgct cgactgccaa ggaagggcac tgtgtgaaag 37380 tcaagcgata cgactacgat gaagctgaga tcatcgacgt ggaagagttg atgcacaaca 37440 acaatgaagc tttcatcaat gaacttggcc acacggcccg ctccagccac gcagaaaacc 37500 tgtcgccgtc cggaatggtc ggtgcgttag tctgccgcaa cgaacgtctg tggcctggag 37560 tcaccttcaa cgtgtcggcc tccagcctga cccacgacga gaaacagcgc cgctggaatg 37620 acagggaata cctcaagggc caggtcatcc gattcaagca cttctcccat ggcgccaagg 37680 acaagccgag acacgccgtc ttcgattgct ggctggacgg atggggcgga agccactgat 37740 tctagaggac actagatcga aataaacccg gacgccttac cctacaggcg atccgggttt 37800 tctcgtttta atgtcgacaa attaggcctt agaccggacc cggccgccag agttccttgg 37860 ccagaaagaa ggcgatttaa tatcgcggtg cgtatcgtta aacagttaag cgcgagcatt 37920 ttcgacgagt tataatagcg cccgaacctt ccgattaaca cagcgcatcc ccaagccatt 37980 atcggggtga ggagaagacc gcagacagag gactaaacat gaaacgcaaa gagcatcgca 38040 agcgctttcg gccaagaatc agccccagac tccgggaaga gttaatatcc gttctgacca 38100 agatcatagg cgagacagtc aaggacaagg tggtaagagc gctgttaatc ggcgttctga 38160 gttcactagg gaactatgtg gattcggtca ctcaggaaga gtccgccgcg ccggttgaag 38220 tcaagatggt tgaagaggca aagccggaaa gcaaaaaggc cgctgaataa gcggcctttt 38280 cttttgggcg aatatcagga gccttgattg atcgcggcga tggtcttcat atagcggttg 38340 atccggagct ggccatggtt cgcatcgttc ggcgcggcgc cgttgatggt tttcacgacc 38400 atggagaagt tgttggattc cgccatgggg atgcagcgat tgcgccagaa gaaccaggcc 38460 gaagacatcg acgcgccggc cggagtttcc agaagctccg gcttctccag aacgtccatg 38520 ccggagtctt cggcgaacag agaatagttc gacttcccgg tcagctggat taagccgcgc 38580 ccgcgatact tccaccatc gccatcctgc tcgcatccat tacccatgcg atccgcgtac 38640 acgttgttgg cgatggcaac cgggtttcgg gccagacgat tcgccagagc attcgggaca 38700 tacgggcgga ctcgcgggtc tactgcgtac cggcgcggcc atgtgttggc caatccttgg 38760 gcgctgtagt tgagattctc caccagactc accagtccac cggactcgac gccgatgttg 38820 gctaggtagg ccgcaatggc tcgcggcgac tcgatgtgga acttgtccat ggccgcctgg 38880 acatcatcca gccacttgat cgcccgatcc gtggtgcacc cggttccggt gataagaata 38940 tcctttgtga ttttcatcaa tactcctgat ttttgaacat cgttttcaga gccatgggaa 39000 gtcgcggccg atccccgcta ttccaatcgc gaatctgctg cctccagtga acaagggctg 39060 ctatcaaccc aggtccgtcc gtggtttcga tacccagccg cctctgctcg tcgtgacgat 39120 ctatgggcca gcgggtatca cgaaggatag cccgcttttc cctggcccgt atagcgtcct 39180 gcaaggcctg ctcccgcttc gcatcgaccg gggcgatagg tccgtgcgcc ccggatagga 39240 tcgcagcgtg gatggccctt ccgtgggcct ccacgtcgtg cggattggcg gtgaaaggaa 39300 cttccccgat cccatcgaaa gtcaccatgg cgtggatgtt tgttttatcc agccaacgag 39360 ggtttctgat ccgcgtccat ttcattttac gtcactcgct ggaaaagggt cgcggagtca 39420 ggagtgttgg catcccggtt gactacatat cccatgcagc gccaagttcc ggcaggcctt 39480 tgaccgctat tgtagtttgc ggcgcaagac gagtagatga gaatggaacc gtccacaacc 39540 actcccggtt gaacggtcgc ggttggagcg gcattgtcca gaaccgcaaa gatgccatag 39600 gaaccgactc cgccaagacc cacctgaacc agcgcctggt tgatgtagtt attgtagttc 39660 ccggcgtgga tgaccggata ggcgtttgcc cccaggtttc cgccacctac tttgagaacg 39720 ttgtcggtat ccaagccgaa gttgacgaag atactgccgc cccgctcgaa agtgactgcg 39780 gccgcttgcc ccgaatgcgc cccattctgc aggttgatgg cgccaactcg accggacgaa 39840 gctatgccgc taccagttcc agaaatgcgg ttgaagacca tgttgccgtt ggtggcgttc 39900 gcggcgttca aatccacttt cgtcgccgga tcaaagtttc cggatcgcca aacggtttgg 39960 ccgttccagg acggcgcggt cgggttggcc gcccaaagat tcatgatgtt gctggaatcg 40020 gcgatttccc tggaactgtt gccgagcgat ccgccgcccc atttcagctt gttgtcggta 40080 tcgatgccga agaacgcgcc ccagttgcca ggacgaatga acgcgatgac ggccggtttt 40140 gcagacggac cggttggcga gttgtaaacc gtcaaagggg cctgagaata atcggacagc 40200 gatgcgattg gagcgaatgg catagttccg ctgaatatcg cagtgctgct agtttcctgg 40260 gtgccggctt tgatggtcag cttggtgttc ggattaaagt tccacggccc ccagaattcg 40320 tttccgcccc aaacaggagt gccagccatg gaattcacgt ggaaacgaat gttggattcg 40380 tcggtaatca cgtaggcgtt attgccgagc gaccagcctg ctcgcttcag ctggccgtcc 40440 ttgtccatgc ccaaatacca gccggtttgg gagttgtcga agtagatggt cgcaggctcg 40500 ccaccccctc taccgaagat ttgaatggct gcgtttccat acgatgcagt tgtggagctg 40560 gagccccatg tgttcatatt tccggtattg ctggtggtat tgcgaattcc ggtcggtccc 40620 gaaatgttgt tggtagtccc gacagtgagc ttggtggccg gatcaaagtt tccggagtcc 40680 caagggacat attgtccagc aaacagaggg cgattgttga atatgacgtt cgtggacgcc 40740 cagtcccatc gcatgatctg tgagcgatag gagccgtccg gattggtggt attgactgcg 40800 ataaccgcgt tgttgttggc gtccacacct tgtgcgaagg tgaatttcca accaggctga 40860 tcggcagtgg tgttctgcca aaggggacca gagttcgcga tgtacgcgag gtttttcgca 40920 acatccagtc gcggctggag gaatgtaaca ttcgacctgc tgaacaggat atcctgggta 40980 ggaccagcgg acccctggcg agagtagaac gccatcgacc catcagcttc agagataaag 41040 cgatagtcga agtctttggc gcggttgttg ttgaagtgga aatcgatgaa aggccgagcg 41100 tcagacaact ccagattggc gaaccacggc gtagtgtctt ggatagcgac gttcggcttg 41160 ttgacgacgt cagcccagtc cacttcagtc agcttttggg acgcgacgta atccttcacc 41220 tgtttccagc tgggggcctg gtaatcttga tcggcgttgc caacttggat gcgtggcgcg 41280 cctgcgagga ttctccagcg gtcgcctgct gcgtcgaata caagctcagc gatgagtcct 41340 tggccaagtt cgccgccggt gagagggaag ttggccgcgc cgacgatggc tttggcgccg 41400 agtccggaga cgttgatggt ggaggcgccg gtgttcatgg tgttgaactt gacccgaaga 41460 atcatgccat ccaccaggcc gccttggagc tgcggaacta gcgtcaacgt gtaagcgttc 41520 gccgatccgg ccgcgactcc ataggtgacc cgaccttgtt gaagggccat gacgtttacc 41580 gcatacatcc agttggtcca cgctccggca ttaagcccgc gcacagcgac gttcccgacg 41640 cgatcagtgt agcgttggac gcagaacgta ttggctccgg acacccaaga tttcgcctcc 41700 aacatgccag cagcggcacc agcggaagcc ggatatatgg gggcattctg agaagcgata 41760 accactgaat cagagaagaa ctcccacgtc ccatttaaca ggtcgttgaa gttgcggccg 41820 gtcgtgatga cttctccgcc agaagatagg cctgggcctc cggccggcat cgggatgttg 41880 gagcgcatcg ccgaccatgc gggttgttct tcccaagtcg tgctgctgag agggtcgctc 41940 gcattggcat tcaccatgga acgataacgc cgcattatgc cgtcatttcc gacgcgcacg 42000 acttctgcat tctgttcgta gccgccaggc atgccctgaa accacggcgg cgccatttgt 42060 cgctgccacg cctgtgcgtt ctgggtcgcg atgaagaaga gttggttttg aattttccgc 42120 tcgaccgctt tggcctgcgg gttgttcgac gccagactga tttcatagtc cggcgtatag 42180 ccgtcgcgaa ggtttgcgaa gccagtggag gaggtttgtg gaatcgggtc tttatcgccc 42240 tgagcggcaa acggactggg gatcagttcg ggtgtgatca cgtcattact cctgaatgac 42300 tttgacatcg caaccggcgc aagtcggcat aataccaact gcccggtcat tcatgaggtt 42360 gatcaattgc ggcgacagat taagcgccgg accaaccctg tattctagct tgaacgcccc 42420 actggtgggt aggccgatgt atgcggggtc tgacagagta aacgtatcct gagtcccatt 42480 cccgactgcg aatctggccg gttctgctgc agtcccgcct ttccagtctc cagtccaata 42540 cgcttctact ccggtcggaa ggggctgtgt gaacttgact gttccggtct gggcgttctg 42600 caaaacataa tcggtgatgg ttacgggcgc cccggtagtc ttcaagtatc cagttggagt 42660 atcacccagt tcgatctgag cgccccagat gagcacgtca atcgccgcgc tggaattcga 42720 atcaatccag ctgaagttgg tttctgccgg agcgacgtaa gcagcgcgga acgaagagct 42780 gcggtcttg gtcgtgagaa cgcaacgcca ccagccattt tccagacgaa tcattcgggc 42840 gcttaccacg ctgctgtcca gcatctgatc gctgattacg ttcccggaat ccaggtcgaa 42900 aacggcatcg gctcgactgg ggaaatcggc agccgactga attgcaatga aacgggtgga 42960 gccggctttc gcgaagaacg agaacgttac agtgctaccg gaccccagcg gcccatctat 43020 cggcgcggag acgtaagcgg tactcccggc cggcttagta agcttgcaca ccgtagcgga 43080 gccgtccggg gccgtagcgg acgccgtttc gaccgttacc ggaattccgc tcgcggccgg 43140 atcgactcct ggccaatcgg cgtcgctggc aggggtcgat gtcagcacgt ggttcgttct 43200 gggcgaactg gacaacaaca ccataccttc ccaatctttc cgatatactg ccaagttctc 43260 cacagggcca ttctcgccgg ttgagtccat gagatagaag tacagaccgg tcgcctcgtc 43320 ccatggctca tcatcattga atatgtaacg aagcatgcga ttgatatatg caatcgagcc 43380 gttcgaaatc agcgctacat atcttagctg aagcactttc ctgatttcgt ccaagttgag 43440 aatttcggca ttgccgccac cgtagaagtt gccgccaggc gatgcgtctg ccggtggcgg 43500 aacttgtgta ccgctataga tgaagttctg gcgtagccga ccgaatgccc aagaactgtt 43560 ttttggataa aggccgaacc ctttcgaagg cgtgccgagg atgatgcacc aaaccataag 43620 gccgaacggg ttggcagttt tcaagtggaa aacgtcgcgc tcccagttgg cccagaattg 43680 gcggctgaat ctgtcatacc attgcgcctt tctctggatc aggccggtga ttccaggcgc 43740 ctggttatgg agccatttca gagcttgttg gatgtccgaa ttgtacgcag gcagagtcat 43800 acgaaagtca cccgaacgtt accaacggaa atggtagcct ggccgaatgc gctcatgacg 43860 tattccgaag tgaaatcgcc cggagccgga gccggcgagc cagccgcgac gcacgcgacc 43920 tggcagagtt tgatgtagat gccgggaatt tcgcgagcga tggcgccggc gacttcgaat 43980 gccgacaggc tcgcgcccac caccagcccc tcttcccctt ccactttccc ctgggcgtaa 44040 ttgaccactg cgttctgaat ggcttccgga gctacagagg aggaaccttg ctggactgtt 44100 acgttaacat atccatcgta catgattggg gtggtccact tcacgacata ctttcgaccg 44160 gacgccggat cgcgcacagg aacgccattc ggaccgtcca ccgggacgcc gttgttcgcc 44220 gcgccatagt cccatggagt tccgccgtta tgggcggccc acaacgcatc ggcgactgct 44280 tgtttatccg ggtttccggc gacgcagacc caaacagcat acggaagggt aaacgagact 44340 ccattcacca cttgaacggc gccggtgttg ttctcgatta cgttcaccga cgtgacgttt 44400 ggaacggcgc tcacatacgc cttgatggcc atagtcgagt tgcggccttg gatggccaat 44460 cgattaacgc gggcattctt caactctgca tcgctcattt ggcggctgcc cggatcgacg 44520 cgagtggagg cgatgacttt cgctccggac catccaattg ttccgtcgat gatgatgaga 44580 ttcccgaccg gcagaggaat gttgccatac tcctgcgatt tgatatcgat ggtcgcgaca 44640 ccaccagcag ggatcgtgac atcgctcatc actgtgaaga tcgcgccggc cggagtctgg 44700 accctagacc cggtggaaat gcgggtttgg ctgcggccgg tgacttgaac tccatagccg 44760 aaggttgaca gatcagaacc gcgctcgatc cccatcaagg cacagatcgc gtccaggaac 44820 gttccgaatg aaacgttcgg gtttatggta ttggcaattc gcgcttcatt ccgcatgaca 44880 ctggaacggg cgatggcctc ggccgcgaca agcgatccct gcggagtgct cgcggccaag 44940 ttgatattgg caccgagggc ggcgcggaac tcggcctcaa cgtcactcag aacgtcggcg 45000 gtatctgcga ctatcacacc agtatcgacg atgtagttgt agttagccat tacaaccccc 45060 ccccgctgtt aaatcagaaa aatcaaaact tgccatgaaa atctccttaa gcaatcatgc 45120 cgcctttcgt ccgggcatca ggcgggttgt tttcgaggtg gccgtggttg ttcacgttga 45180 ccccgtttac aaccagggtg ttggcgatag tcacacttcc agtgaaattc gcctgcggag 45240 tatccacggt gacattcgac ggcgcagtga tcttgatgtt gtcgccgcga atcgaaattc 45300 tggtcgctcc ggaagtcgat tgtatgacca tagcggccga atcttcggaa ttgatggtgt 45360 atcgacggaa tacgtccggg atgaacaggc catgctcgaa cttatggatg cggccggtgt 45420 tcggcttcga cattgacaac gactccagga actgagacgt gtcgcggtcg gccgcataaa 45480 tccagcctat gtcaccttgc tgaatcggga agcttatgtg gaagccgcca gcccccatgg 45540 aaattacagg aatatcaacc agctgatgcc tttggacggc gttgtgttcc gtgtcaaccc 45600 aggtgatgag aggttgaatc gtcgcgatat tctcggccct gtcatattga acaacctgag 45660 ccggtatcat tacttcgaaa tctagagcat cccgccgcga ccgagcgtca agagcggcga 45720 tcagtcgcgt cctgtcggga gcttttgcgg atgttagaga aatattggac atgggaaagc 45780 ctctgatttg gcaggtctag tatagccttc ccaggcccgg ttaggaatta tccctttttg 45840 attctgttgt gcgatgcttc ggacgccaag gcctcgttca cgctcttcgc cgtcatgatg 45900 tctatcatct tgaacgcatc ttgagtcgaa taatactctt ccaactcgcg catagaggct 45960 gagccgttcg cgaccaagct cgcaactaca gaaggtgaat gtgccgtctt cacgcttttg 46020 atatcttcga caaatctgga tggaatcttg actccggtcc agtctttgag aaaaccaaag 46080 ttccagtcga ttaccacttc ggacagaagt gcaagaactt gtacgggagc tattactttc 46140 gctcgatcaa cgacataaag attgatgttc gcagcagtca atggaagcca gatgccttcc 46200 ggatggtctt ccggatgcgc caatacatcg gtgcacttga gcaattcttc tggcggcaca 46260 ctctgaattt ccgacatcat gctgagccca tcgacagcag agaattgccg cgaagtatag 46320 tggactccga acatgttgaa tgatttgatt tctctggcca ttatgccgct ggactcccca 46380 tgactttgat atagaacggc cgatcacgac tggccaaatc gtattccaga gcagtaatca 46440 catagttacc attgacgctt gggttcatga gcgattcgac cgccacgcct ccagccacgc 46500 gaatcgatgg ctcaaacaga cactggaatt ccacgcccca ttcagaccaa gatggaatac 46560 caacaaacga gttgacgttg gtcacctcat ccggacgaat gactttatct cggtccttca 46620 cgatcaatat gtcatcatcg acgaacgcgg ccacgtccgg catgtacatg tcctgaatcg 46680 acgccaggat tgccgacgcg acagtgatag accggcccgg attcttcaga acttgatcgt 46740 tgtaactggt atcgcagatg aagttcaatc ccatttcgtt cgcgccccac tcgacgaact 46800 tgacaaacgt cgtgttggcg ggcggcatat tccgaatggt cttcgtcctg tcgatttgcc 46860 tggtatagca ctggatgcgg attccaatgt ccggtggcgg agaaatgata tcgacaatgg 46920 caacttcgcc gacaaagact ctggaaactt gctcgcgccc ctggtcagag tagccggctt 46980 ccaccgacac cttgatcatc aattcatctt ccatgcccac ttgacgttgc cgatgcttcc 47040 acgcggtgaa ctgcgacaga agagactcgc gaagctgagt ggtgaggccg aaaatttcca 47100 tcgtcgcccg gttctgaatc cgcaacgcag ccttcataat ccggacccga acatccagat 47160 cttcgcggat gacttcgggt ccataaggca tgttgaatgt tactcgcaga attctctttt 47220 tcatcagtag agtatcttag ttgcggaatc gttttgagcg tcctggattg ccgtagtcag 47280 ctggtctgca gtctgcttac tgaatatctc gcgagcctct tccggagaat tcgcgccggt 47340 gacgttgacc aacatgtcga ttcgaccgat ggtcagctcc tggccgcgct ctggagcgct 47400 cttcagaagt tgctcgccgt acgtccggag aatatccatt tctcgcgatg cggcgttcac 47460 cttggccgtg gcttcggcaa gcttggctgg agacaggaat acgttgttgg cttcggtcgc 47520 ggcggccttg atctcctgtt gcttgcccag gatggcttgg ttgtatccga acagcaagtc 47580 agaacggctg atttcgcggc gcatgatctg gtttgggtta acgccgatca cttgcgcgat 47640 ggctccggca gtgagttgag cctggatgtt ctgcttggtc tcgccgcgaa cttgattcgg 47700 gaacttccgg aatccagaat ctgcccggtc ggcctcttga cgtctagaca tcttgaggat 47760 ttcaccgtcg ctgcggtctg gcatgcggtc gatgatgcga atctccggtc gcacaaccct 47820 gtcgtcatat cgacgggctt cgcggcgctc atcttccttc ttgccctggt ctggggtttc 47880 cagtcgcccg ccatcatagg gacgaatgtc catgtcgccg ccttccgggg cgaacgtctc 47940 gttggcgacg gtcatggccg cagccttctg cttgcgctga gcctcttcca tcagctcgat 48000 tggagcgctc attaccaaac ccggatatgc gcgagtcctt ggaccccagt tcttcggatc 48060 gagtccgcca tgatagtagg tcaaggccaa ccgcatgtcg ccatttgctc gatctaggtt 48120 ttcccgcagt aggcgcgttc cgccgaggat gttctggcga gggtcatata cgtcagtgat 48180 accatacgcc ttggcgattt ccggcatcag ttgcatgagg cctttcgctc cggcttcgct 48240 gt; aatgttgtac atcttcgaag catctttgat gatatcgttg atgtacgatg gaacggtgac 48360 cggctctgcc ttgcgctgcg gcgagaacat gcgattgcga agagactggg cgccgattgg 48420 ctcgccgaag acttgtccgg ccgcgccact cttcgactga tcatagatcg cgtgcggata 48480 gacgccggtg gcccgcgaag tcggcgcggt gcttcccatg ccgaccgccc gaccaatttc 48540 ccccgcccag gctgcccaag cttggcgctc gtcaacggca ttcgcgaacg acgataccgc 48600 gccactgaac atgttgatcg ccaccgcaaa atcattggta gacttcgtgg tctggtcagc 48660 cagcttctct agctctttca tggacttagt agccttgtcc tggtcttctt gtttcttggc 48720 caggtcttcg ctggtttgag cgccgggaac cttgtccttg tcgatgagcc ctgattcttc 48780 catgccgcga cgagtccccc acgctgccag gcgaccgagc agggcgccgg ggctgaggag 48840 ggataggata tcactgccaa cggtcgcctt cccgagcact ccatcttccc aacgggattt 48900 ggtgtccttc gcgaagcttt ccacttcatt gggaatagcc tggactatct tgtcgatgat 48960 ttcgatcagc ttggtgaacg caggcgcgag cttttcgccg actcggtttt ccagggtagt 49020 gaacgtctgg ttgagattcg ccagggcatc gttgaatttc tggatgttgg actcgccctg 49080 gaccctggac tggagttccg cagtcgtcat ctcagtgact tttcccatgg ccgggccgat 49140 cttcgccagg gtgctcaggt aatctcgcga gacgccaagg gcatcagcgt aggcagaaat 49200 ttcgtccggc ttcagcttgg ccattttcgt ggccagatcg gtgatgatgt cgttgagcgg 49260 ccgcatgccc ttttggaagc tcccgacatc gacgccggcc atacgcagaa ttcgcgcttc 49320 cgggccgact cgcccgatat cgcgataagc acgccggaaa gtgtctgcca gatttttggt 49380 catctccgcg ccctgctcgc ggctgatggt tccaccggac tggcgaacga attttctctg 49440 gtactcttcc aagcgtgccg gggcgatgcc gatgtccatc gcctggatgc gctgctgatt 49500 gtactggtcc ctggtgttca tgaacgcctt gacgccggcc gcgaccaggg ccacgccagt 49560 ggcgcctatt gccagttgcg cgttcattcc gcgaattgcg ctcgtcacag aatcaatctg 49620 cggaacgact ctgccgagtt cggtggccgc gccgtctgcg aagtggcgca aatcctgaag 49680 gccactcgtc gatgcgctgt tcacgcgcct gatctggttc tggaggcgct ccagattgcg 49740 ctcggctctg gcagtatcgg cctcataccg aagtatgaat tcatccaaat cactagacat 49800 gaatcactcc ggcttgttgg cgagtccttc ggcgatcttc attgctggac caatgagctt 49860 ggacgcctcg gccagaaatg cgatggccat ctgcgatccg acttgttccc aatagtccgg 49920 ccggtcggcg tgcgtggccg ggtcgatgcc attgtgcttg agaacagagt tgaaaaccag 49980 ttccacgttc ttccagtggc cgaggtggtt gttgatgact gccgcggtgg tcagcggaat 50040 gccggcgtca tcgtcgccaa gcagcacttt cgcatagccc aggatttcca tggtgaaaga 50100 gcggcggaag tcggaatctt ggctgacagc aaattcgacg aaacggcgct ggaggtccca 50160 gccatccaat gccgaccacg cctcgatttg tacgcgagtt tgacggccat cgggaagatt 50220 gatttcaagc atgatacatc ctcagaagta gctggtcacg cgattatata gcgattttgc 50280 ggccgaagat atcgaatcgc cgatggcgcc caaatccagc aaattagcat cagaaagaga 50340 ttgaatctgt accccataag tcggactatc ttgagggaac gcaggatcga attcattcaa 50400 tactggaggc tcaacctgct cgaattccat attgatctca gccgcgttca acatgtctgg 50460 agactgatct acatcgagcg ccatgatggc cattttatcg gccaatatcg acttagaagt 50520 gatagcgaaa gtcgaggtgt tatcattgaa agcgttcatg atactttcaa cggtggacag 50580 gtccggacag atagcattga tgcggagtcg caccggttgg atgatctttc cattcttcac 50640 atcaatgtcc agagcttcgg tgtacacttg agcttccgtc tggtctttcg tcgccagagg 50700 tttcgacact acggaagccg gcgagtaaat ttccactttc ttgacttgaa gactcttcca 50760 gacaggaagt ttggtaacat cattgcgtat ggtgagagta ggcgtgttga gaatagactt 50820 gaggaaagag ttcaattggc acctcagaac aagtctgcgg cgttctggac gccgtttact 50880 gcgtagtcga acagatcgcc ggccgagcca accacgtctt cagctagggc cagccctcgg 50940 tcgatcatag aagagtcccc tgcatttctg aacattatag gcttgggatt ctggacgaga 51000 acttgggaga atgtcagccg cgcaggagtc gccgatatca tatccggagt ctgattgagc 51060 gcttcgctgg tacacatcat ccgttcgaat accatgccgc gagtgatgac tttgtacagt 51120 gtgtcgcgat ccaggagcaa ttgattgatc tgatcgacga catcaattga agggcaaaat 51180 acttcgacga tgatttccat agggtggatc gttctggaat ccatcttggt cgtaccatct 51240 tccagcatgt ggcgttgccc tacagaagaa aaccgggtgt tgacccggct tatcctcaaa 51300 tccgcagcaa ctagctggtt tgtgttttgg tccacaatcg aaaaagatcg cgaacttagg 51360 aggctggtga aaatccccaa catcagacca cctccagcac cgattggata acgttagaaa 51420 tggcttgacg cgcagtctgg gcgccaagat agctaccgaa aacaaaagtg tacgtgttgc 51480 ctttgcgtcg tccggtgttc tgtatggtgt cgatggccgg acccttgatg atagtcccat 51540 tggacagaac ggtgcggccg ccatcaggaa gagtggccac gagagtcgtc atatccggga 51600 tgctgcccgg aagaaatctg aatgatccct ttttggaatt gagaaggatg cgaaggttaa 51660 tatcatcctc gctccctgcg atgacggata cagatacttc cagaggagca gccttgtcaa 51720 aggcgaatag gccgccgtca taaagcatct catatccgaa cggctccagc tctttggagg 51780 atatcggact ctcatcatca gcgaacttcg acaaggaaaa ccccatcggg aacgatgagg 51840 ctgaaactat tacaattcct gtgccgaagc cgctgacgtt gatcatgtcg agtccttact 51900 tgctggtggt tttgcgagag gtggccttgg cgggagccgg ggtttcctct tcagcggccg 51960 gcgaggccgt ttcctcggcc ttttctaccg gggctgtagt cggggcttcc tcggcgcctt 52020 tctcgtcgcc ttggcctgct gcaggagctt cctgggcgcc ttccggggcc gattcggccg 52080 cagcagcatc ggtcgatacc ggagccggga tggttccgcc gttgtcgaca ttggaatcga 52140 cgtttaccgg gggaacggga agaccggccg gcgaggagtc gcccttgtcg gtgttctttt 52200 cgcggtccag gccttccaga tcttcgacag acgggttaaa cgagggcagc gggtccaggg 52260 gcggcggatt tttgccgtcc agaaacagtt gggtgccgtt ggcgtattgg atgcggatgg 52320 tactcatttc aaactcctgt ggtaacaggc ccgtggatgg tgatgacttt cgcatcgacg 52380 ccgaagactt ccccggtgat gtcgatgtcc agctgctcga tgccggtcac atccggcgag 52440 gacaaaattg catccgcgat ggatttgcga gcgtcatcat agcttttctg cggcgagaag 52500 atgtattcga aatatcccac gccggagttc acatcgaaaa tattttcgcc ggtgcgcatg 52560 agcatcgccg cccgaacgtc ctgggcgcac gcttcgacat ccctgaggat gaccatgttt 52620 ccattgtcgt ccaaaaggat atcattgttc gtcccggttc tgatcgttga tgtgctcatt 52680 ctttcctcgt ggcgagcgcc tgatactctg cgaattcggc gccgtccaga tagaacaggt 52740 tgattccgtc gccgaacaac gtccaatcgg cgtcgcggtc gaagacgaaa ttgccatagt 52800 caggtcggta ctgatggctg tactggagaa gaggaatccc gccgaagcag cggaccccat 52860 ggcaaacgat cacgccgtcg cggctgatat cggcattcat catgtccatg ttctggtaca 52920 ggcgaatctt ccaatagctg ctaccggcgt taaatgagat cgcttgattg gggactgctg 52980 tcagcggaat tttcttcatc agctagtacc ggctttgatc actttttcaa atcggaaccg 53040 atacggcttg gtcttcagac ggccgacgct tgccaccgcg ttgatcagaa cgccgtcgat 53100 gggggtgccg ttggtgcagg tgattttgct gccgtccggc atcgccacga ccagaccgac 53160 gacatcacga gcgcccgact tgtcctttcc ggtgcggttg gcatccagca ggactgccag 53220 gttgcgctcg ccctcggtat tcggaatgac gttgacgact acttccagga tgttcgcccg 53280 gttccaaact accatgtcac cgttgagacc gacgccggta tcggcagcgg tgaacggcgg 53340 gctgtcgatg ggatcggcat cgtcggcgaa ctcggtgacg gtgaatccgt tcgggaaagt 53400 tctgcttgcc gtgaactggc agatcgagcc gaacgcagaa atgttgatca ttgcttattc 53460 ctcactccat ttatggaagg tcgcggcgga tcgagtccgc cgcaaaccat tagatcatca 53520 catccgaccc ttcgacgaag cggatggcat cgcccttcga atagatcagc gtgtagttgg 53580 ccttccactc ggtcaggcca gtgttgctgt tggtatagct ggagaaggtg atgttgatcc 53640 agtaacccag ggtttggact tgacgccagg cgcggcgatc accggtgact tgggtgatgt 53700 actgctgctg gacggcgctg atttccttgc cgtaggtgaa cgtgccgttg gcagtcgcct 53760 tgtccagaac cggctgcagc accgccaggg tcatcgcctc gccagtgctg ctcgccggaa 53820 ccgcattgac gttcaggaac agatccagga gcgcttgagc gatagccgac ttcagccaga 53880 tttcgttggc atagacgttc atgtccaccg catcggtcgg accgccgcac agaatgccgc 53940 gctggtagaa cgcgagttgc tggccattgg cctgggtgac gccgatgtag ttgccccggc 54000 tcttgtcgac ggtgttcgca acggtatcgt cggaaacggt gatgttgcgg ccagggaatt 54060 ggtagtacat gtagttttgc gaagcgcccg gctcatcgta gttggtggcg gccagaatct 54120 cactggggca ctgctccacg aagtcgttgg cagcagtcgc cgacagcacg ttcagggcgg 54180 tcccggcgtt gccattcacc aaggtgaaaa gagtgccgag gttcgccagg gaagtagcga 54240 ccgtgtagat gaactggttg ttctgagccg cgttccaggc cgacacggcc ttgatctggt 54300 cattgtcgag cggcgcaccg gcgaacagga acgaaccgaa gttgttgctg acattggtgc 54360 tcttggcaac ggccgcgtcg ggaagatcgg cagcctggcc ggcgacgttg acgacgttgg 54420 aggtggacca gccgagggca gtggacatgt cctgggggtc ggcagatttc gccacggcca 54480 gaacgccggt gccaatggtg gcgccgacca aggtgaactg gttggtgttc tgattccagg 54540 taacggtagc ctgggccagc tgcgggtcag cgttcttgcg gatttcggtc tggatgatcg 54600 acgccacgtt gtccatagaa gtcgcggcgg acgtatcgat ggcggtgatg ttctgttcgg 54660 ccgcgccgac catgatggtc agaacccctg ctgagaagcc ggcgaaatcg gcgatggtct 54720 tcggcagatt gtcaccaaca accatcggcg cgatggcggt gtttacccag cgagcgaagc 54780 tgatgctgga cggcgaattc acgcttttac tgatgaattt gaaataagcc gcagcccgct 54840 gatactcttc tgactgcgcg ccgaagtatg acaggactgc gttggcgttg tcgaactcga 54900 tgacgattcc gggcgggatg acgttgttgg tagtcatgac gcgcagaatc agctttcggc 54960 ctgcgaccgg agcgcctgcg cctacgcccg aaatgatccg gatataacgg ctctgactga 55020 tcactggatg atctcctggt tatgttactc tgctgctaat cgattgaagc atgtgcgccg 55080 tatcgaccag cggtctgttg aatccctttc tcctgaccgt agatgctgag ttagccaccc 55140 atggcccggt cctgatgctt ctggctatgt atccttccaa tgccaggccg atctgggcaa 55200 gagcttgatc tggagtgatc tgtcctctgg ccagcctcat ggctatccgg ttctggattg 55260 cggcgcgatc tgcggaaaac agattccaag catatcgcat aaacggtcta gccgggatgg 55320 taattctgtg aggcttagtc acctcggttt ctcccggaaa gtcgtttctg acgaaccgaa 55380 cgccaacaaa ccggccccga acaatggcgt ccctaatata cctggtcccg cccggatggt 55440 cgatagttcc gccgtactca ttgagacgtg cgattctcgc gacttgtatt ccgaccgatc 55500 cgcctgcctt gtcaggatat cgagccgtgg aataccatcc ggctgaaacg gacctgccgc 55560 gcatggctct taacatctgg aggtgcgcgg cgattagctc tgaatcgcgc ctcagactca 55620 tatgcctatt aataccccat cggccgaata tgctgcgttt tcgtacaggc gaatatattg 55680 gttgtaagtt acaaccatgt caaaacttgg gtggaattcg aactggtgat tgtcgttctc 55740 gaatgcttcg ttggaaattt gagacacgcg aagaatgagg aagtccagtt cctttacgcg 55800 ctcaatcgtg gatcgagctt ggaaataagc cctcacatag ttggcgatat cagaagccgt 55860 aaccacgtga gttatttcag gattctgcca atgaagggaa ctgatctgga aagtcgtctc 55920 tacatgctgt cgagttattt ccacatattt gcgggccgtg ttgtccaggt accaatcggt 55980 ggcaggccag ccgcgaggaa tgtcaaacag tttctggaaa aagatggtcg gcctggttga 56040 cgtcccctgt tgggtcggct gagctttctg gacgacttca aaatccggga actgcaaagc 56100 ctcttgagca gatgccatcg ccgcattcag ctcgacaacc attttcgcta tcagttcgcc 56160 gtcaaacata caccacctag aaagtcggtt tcccgtcatc ggtgaacttg gccgcaccga 56220 tatccacggc caggcaaact ccccagccgt cctgataaaa ccaggagcct tgagactcca 56280 gctgaaaaac tcttccagtc cagaggaact ggtcaccggc catattgcga tccaagtcaa 56340 ccatatcaaa gttggcgaag atcataacat aattccgttg gaactccaga ttaaactggg 56400 catactgatc gcgtcggact cgctggacag acgctgccag gtcgaaaggc tccccgaaca 56460 tggagacata ctgggcttga tcattcttca ctcgctgctc aaacttgcga tatttcacaa 56520 tttgagtacc gatgaccccg aaggccattc gcagaagatt cgcaccaggg atcaccagaa 56580 cgtccctcca accttccgga agcctcggcg ctctggaaga ccgccgatgt agaatccgcc 56640 caccgctttg acgctgagga gcgcccacaa ctcttggcca taaggcgtcc cggaaagcca 56700 ccactgccaa ccattcttgg ccgggggcgc gagcttggcc acgctgacct cgccgaccgt 56760 agcgctggtg atgaaacctc cttgggttcc accggcagtg acgccacctc cagccgcgcc 56820 ctgaacttgc atcgtggaca gcgacaggag gtgggcggtc agaagataca aacaggcttc 56880 cagggcttta ccattgagaa tccggtatgg cgaatcgcga tcagaaatga attcgcacgc 56940 aatgtcgaaa tacatctgca ggcgcacgtc cggataagcg actggatcag caaactccgg 57000 aaacagcgtg cgaaacttat tttcgtcgaa aatcaccata ccgaaaccct cggttaaatc 57060 cggaactctt gttcctggga agcgctggcc gtggtcacct tgattttctg ctgcaggcga 57120 gtagcgtcca gaggctggaa tccatcgcgc tccatggtgc gagtctcttt ggaaatccgc 57180 tggtggtcac tggtgatgtc tgtcttcacg actcgcagat aacccttatc catgtgacgc 57240 atgaaaatct tattggcctg aagcagctcg aaatccgaat cgctcacggc agtgcaatcg 57300 ccctgcgggg tccagatcgg acgcccggcc gcgtcggaaa tcatgtcgcc gaagccggaa 57360 gtttcggatg caatgccggc gcggccacga atcagaatct ttcgctggag gcgaggattg 57420 gacggatcag aggtgtcata cgcattgtaa gacacggatt gagtcatggc ggaaacgatg 57480 taaacagtca ttggcgtagt cctagtaatt atgccctaac cggcccctac aaccgagtca 57540 gagtcagagt gaacaaaggc cggaaacccg gcctttggtg aataggcatc ggttagatgc 57600 cgaggtagcg caccacggcc cacggacgct tacacagcgc accagcggtg ccgttggaga 57660 agtcttccac atacgacttc gcccgctttt cgacacccag ggtgatgaac ttgctctgta 57720 ccagctggct gaacacgctg ccgccatcgg tgcttccatc gacggccgcg ttcacgtctt 57780 cgacgaagag caccagagca tcttccggct cttgggcttt catctggacg cctgacagtt 57840 ccggagcaga cacgatccgc attttcggat aggtctgttc gatccagtca gaaaccgaaa 57900 tgccgtatgg cgtggtgacc gacaggtagt ccaccttgct ggtggccagg gccagggtga 57960 tcttttccgc cttcggatcg atctgatctt gactctgaat acgcagctgg cgaacggcct 58020 cgcggatatc gccgatgatg cctgcccagt cggcagtgga ccagccatgg ctcggcgggg 58080 tctggaacgg cggcaggttg ggatcgttca ggaaaccata ggtgcggttg cccaggccgc 58140 tctgccagcc ataaaagccg atggcgttgc ggaagatttc cagaccgatg gccgcctgtt 58200 ggcgtttggt ttcggcgctg ttcagccgga tggccgaggc acgaccctct tccagggtgc 58260 caaccatcat acccagctcg ccacgaacga tggtgcgacg ttcgaagttg gcgttccagc 58320 tggtcagcgg gatgttggtg tgatcgccgt attccaccgc agtgccggcc ggctccacga 58380 tgccctggac gatttcttga tcttcccagg agccaacggt atcgatgccg atgatttcgt 58440 cgatcttccg tgcagcggtc atgaccttca cgaagcctgg caaccaggtc tgcaggaact 58500 ggatgggagt cgggatggac ggcgtggtca ccggggcggt gaagttgctg tccatggccg 58560 agccggagcg gaacgcgccg gccttcgcca aggccttgat ctggtcctgg acgacggcgt 58620 gatcgaatac caggccgatg cggcgcagag acgccacggc gtcattggtg atgtttttca 58680 ggtcgaaagg tttcgcattg cggcctgcga ggcgcgaatg ggtcttgctg atctggctca 58740 tgacgcctcc ttactgcgtg agctggacga tggtaacgcc agcaaccaga ttccccgccg 58800 actgggccgg cagactgatg gcgttaacga tgcgtgcgtt gggaatctgg accaagccgg 58860 tcggcatgga gccggccttg aagcccacca gggcgcctgc cggcaggcca agcgcgttgt 58920 cggcggtagc caggttgttg gggacatagg cgaccaggtc accatagtcc aggtccaggg 58980 cggttgcggc gccgttgaaa atttcgacga ccaggccggt ggccatatcg aagaactcgc 59040 cttcggcgcc atcgggcaga tcatagctgg gagccaggga gtctccggcc gaaccgaaca 59100 gagcatagtg cttcggatga ccgaggacac caaagaagtt ggcgccgccg atcacgactt 59160 cagaagcacg agccgcaatg gtcttcggct gaccttcgcc gagggcgctg acgtcaccgg 59220 cataaccgaa agcgcgactg atgcggttgg ggccggtggc ggtggcagcc ggagttacgg 59280 ccgacagagc catgattcga cccggccgcg cccgcttcgg gccgtcctcg atcagatcgc 59340 ccggaaaacc aggagtgtac tggcggtaaa cttgtttctg gaacatgagt tactccccct 59400 tcaggtagct gtccagctcg gcgcactgcg gagcagaacc ggccgaatcc tgggctttcg 59460 attgacggct ggccgcgccg cgcgaggctt cgacgccttt caggtacatg tcgagcgcca 59520 gagcttcctg gcccttcgca cagctgatgt tcagcttttt cacgccgtaa acagcgactt 59580 cagccgagtc catagctcgg tgatcgaacg caccaaccac ggagctaaga cgcttgtaga 59640 ggcgatcttt agcagcaatg tcgcgataga gaccgcgaat tgcagcatct tgcgcgttct 59700 tctgtgccat ttcaggaagt tcctcgctgt tatccttgct ctcaccacca tcgtcgctgg 59760 cggtttgcga gccgctgagg ctgctctgct cctccaagcc ctcgacgaca tcttgacctt 59820 cgccatgctc ttcgtctgcc ccttcggcta ccgtgccctc cagtcgagcc agaatggctt 59880 tgacctgaga gatcagttcg gcgacttcgc cttcaccgga catttcggat gcggcgcttt 59940 cttgatgctc cggctcgacg gcggccacgg ccggatcgac aacggaaggc tcctcttcct 60000 gctcttcgtc atccttctga gcaccttcca gagtcggatg ctcggtcagg tgctcgctgt 60060 cggtcggttc ggccggagct gcgccttcct gatgctccgg ctcctgctct tcttcgccca 60120 ggaacttctg gacggacgca gatagcttcg gccacagggc gcgcaactct tcgaccgccg 60180 agtcagcagc ttgccctacg cgctggacag ggggcttccg cttggctttc ttgagactca 60240 tttcattacc ctcatcggat ggtctgaaat caaaactgag atggtcaaaa cacagaccat 60300 ccaatactct ggcccccggc acacgaccct cttttaccag ggcaatgtgg ttgccgcgca 60360 tcttgtcctg gacgacttca taaggcgttc cgttccagat gccgggttgc tcagtgtagc 60420 ggcaactata gcctagggac aggtcttctt tgcccctttc cagctgattc tgcatgttgc 60480 gggaatagat gcggatatcg ccacgtgccc atggggcttc gtagtaagcg ttggatgtga 60540 tgatgccctc cacccctttg tcttcggggg ccacgctatc gtcatcatcg tcgaatcccg 60600 acagcatctc atgctcgtcg atcaacggga gattcttcag agattcgatg tactccggat 60660 cgctgacggc agactccggg cgatatacgt tgacaatccg cgtcggatcg cccggaagac 60720 cgagttgacc agcagaatat tggaaaacgc cataagagct gatcgggcag ccctctatgg 60780 tcatatatcc attttcgtca atttttcttt tcgactttgc catcgttaat tcgaagagtc 60840 gtggactatg gctgtattat atacgcagta catctaaggg taaataagcg gaacaataat 60900 tagatgtagc cgcgactgtt aacttacatt ataatttgta ttgtgatcta attaccagtt 60960 tcctcagccg cgaaatccgg taatttggtc tcggaaactt gacgggattt gtctaagcct 61020 actgccgcga ggctttcaac tcctaaaata attaaaatta ccaatttacc gattaaaaat 61080 tgaatttcaa tacgtctaga gtatatagat tgacgttata ttataacgtt acttatagat 61140 gaattctatt ggaacgttac ttctaatttc ccaggctata tacttttgaa gcatgcggct 61200 aaatcggaaa ttaggaactg gctctgttaa agcctcgcgg cagtaggatt tccaaattac 61260 tgctattttc cgtaaacggt aatttgcggc tatccggact agaattttta gtcagaatcc 61320 agatttttct cagcattatc ggccaaaagc catcaagatg gcgacgccga tgattgccaa 61380 atcgatggcg gcaaacttca ggctgaagaa tccgccgtga atattggccc tgattacatc 61440 gaccacgagt cggcgccggc acgtcttgcg gttcatttca cgagcctcga cagagcgtcc 61500 accagggcgc gaagatcggc gacgagctca ggcgaacaat ctttcgccgt cttccctttc 61560 tcactgcgct ggatggaata agcgatggcc gcagcctgct tcgggtcttt accggcttcg 61620 atttcccgct tgatgttttc agaacgagcc tcattggaag tgccatgaac taacggcata 61680 tagcgctcct atcgatatca aatgatcggt atctttctgc acctacagtt aatcgcccat 61740 cctggcggcc cctggtctgc tttcggaccc tcccaaagtc tggggtcatt cagcttgaac 61800 ctcttcccat ctttctccag gtgggtgtgg cgaggagtct tgccggcaga agagtgtagc 61860 cactcgaact cctcgactcc attttccgcc attctctcat cgctcagaga actgtaaagc 61920 ttgcttgttt gatctcttgc gatgagttcg attcgatctt cagaaaactt cccgactttg 61980 cgaagtgcgt tagttatgcc ggaagttcct tgctcttccg gattcgggga agtcagagac 62040 agcattactg atgtgtaaat cttctcgtgg acttcctctt ggatcttggt gatgagagta 62100 tgattgtaag tggttgcggc ctccagggtg ttcctgacgc tctcattata cgcagctcgt 62160 ggctgatcga cgccggccac cgacaagctg tgaagggtcg cagcagtggc ggcttcttcg 62220 gtccggttga cgaactccgg ggcgatcttg gccgcgaaac cttcaaaaat gcggctccat 62280 cgctgctgta ggcttcgaag ggtcatcttg aacaggacgt taacggattc gtctctggcg 62340 aagaaccgtt cggccgcagg ctgggacagc gccttctcaa tctcgtttcg atagtcggag 62400 atcatgagct tggacatatc ctttatctgc tttcgatacc aggcctcgat tcctgccgat 62460 ggaattatgg gcttccctct tccaactgga agaggtgccc ggcgctcgcg ctttttggag 62520 gccttgaatg ccatcactcg cccccgaatg gtttggtggt gtcgccgttc gccagccagc 62580 ggggaaagc gggcaggtca acttcgtgga tggagccgag accatcccaa cccggacgga 62640 agcaggacag atatccagac ttcgcgtcat tgatgttgtt gaagccgagc atgcatttgt 62700 gctcgtcaaa ctgcccttcc ttgttcacct ggttgacgac gaagacccgt ttggagccca 62760 gattcggacc gacgaagcaa tcgacttcat ccccatcagc gcctttcgtt cccttgatga 62820 atccgtagtg atgtttcatc tgaactcgcc agctcccatc ctttccttgc cgaatgcttc 62880 cacgcggatt ttcgatcaag gtggttattc cattaacctt gatcctttgg agttccgaat 62940 gatcacgagg accgacgatg cggttggacg aaaacaccga aggttccatg cccgacacgc 63000 cggttggga cgtgcgcttc aggccaggcg cgtcattgtg ctctatgtct acgccgtccg 63060 gcgcctgaat gtcgtccaga tcttggagct tcgacaaaag atcggccagc aagttccgta 63120 actcggcctt ggggtccggc cgcgacggcg gtgcagcggc ctcgctggcc ccttcctcgg 63180 ccgctttcgc gaggggctta gtcccgcgtg gggctgcggg aactggcccg cctgcgccct 63240 ctacggcgcc cgcttgggct tcggctcgct cggcttcgcc ttttgccttc gccgactgtg 63300 caccagcctt ctcgaattcg gccaggtttt ccggagacat gcccggttcg gtttcggcct 63360 gatcgtcggt gagtcggttg tagccggaac gtggatcgtc acgcagacgt tcgcgaactt 63420 catccggaga cacaacgccg gagttgatgt agatttcgtc ggtcgcggct ttcttgttgt 63480 tcaaatcggc ttgttgctgg ctggtcgtgg agtccacagg attccagacg atttccagct 63540 gcacatcgat ttcttccgac ttcgccagaa gcaaatagtg gcgttcgaga agtgggtcga 63600 atatgtgctc ttgaatggac tccagttctt cgtgataaga aatcgtttcg tgctcaccag 63660 tggcattgaa tccttttgga gaagtgccga ggagcttcgt ggctggagtc ttggcgatgg 63720 ccgcgaccag ctgatattgg ttcatgatga tgctgtcgaa gtcggccagg ttcgtgtcga 63780 actgctccat gccttcgtca attcccagaa ctttcacgcc gtggttatca cggttggcga 63840 tccagaacgc caggcgagcg ttgaaggcgt cttcattcgc gatggctttt tccacgtcaa 63900 cgtgaatggt actggtccgc ttcgacatgg ccagcagcgg ggcttcgttc gccgtccgtt 63960 ccgccgcata cacgcgctca tagattctct gggtgagcgg gatgccgccg aagagatatg 64020 tgggcttcag gatatctggc ggctgcggcc cgcgaacgac taccaggtgg ctgcggtgat 64080 attttttccc gctgatgatc cagaaatccg gctcatagaa atgttcggca gacggatcgg 64140 ccgtcgaggc agcggtaagc tgcggcatcg cccaatatgg atcgacctga gagattccct 64200 tgtaggagcc gggcgtgatg ccatccggat tgaacggctt ctcataatag tccggatcgt 64260 cggactccac gacgaacagt gcgatacgaa cgccgaagac gtttttgaaa cggttcagtt 64320 cgacaaggtt gtctttgacg cggaactcca tgtcgcgccg ggcgatcagc gcgctttgtt 64380 catcggatag cttccggccg tccgacttga gttcccatcc gttccgtgcg gcgtcttcgc 64440 cggacatgga acaagccttg tccaccaacc agtgctggga aatgatggcg caagcttggt 64500 gtccgatgaa gccttgggag ttataccaat cctgcagcat ggtcgggacg acatagggat 64560 tctggccgcc cgcagcagcc ttcgcggccg gagtcggtcc gtcaccatac gcgctgtcca 64620 ttgcgacgga taggcccggt tccagaaaat ccttcacgct acggatgacc ggggttttct 64680 ccggctcgac gttccagccg cgaatccttc ccagcttgat catggggtcg agcggatcgt 64740 gttgagggat ttgtgcgact ttctccggcg ccgattcaga acaggcagca ttatcctttt 64800 tgcgcccgaa tatccaggaa agtttaaaca ttgtagttcc acgtggttgt tggctgtgtg 64860 cgcttattat aggggaaaca tcaaacgttc aaaagagatt caaacatata catcagatta 64920 acagttgcaa ctaatcagtt atgagaaaat tattctttac gggaactttt cggcagatta 64980 gactctaatt atcaaccaat ggagattaaa catgaacact cttttgccaa tcgtacatat 65040 cgtgttgaaa gacggcgaag ttctgggcgt attcgattgc gacaaatcgg caagattgtt 65100 tcgcgacatg aaaggcggcg tgctggattc ctggatggtg gaatcgcaga acagctcgcg 65160 ttcacgcctc gtcacgaaag aaagctatga agtcggcgat cacgtcatat acctggacga 65220 gcacggagaa gggcacggca aggttctggc ggttgagccg cgaggcgagc gagctgtcgg 65280 cggacgggag ctgtacaacc tgtaccaaat cagcagcgac gatccgtccg tggagatttg 65340 gatgctcgac gcagacatca tcggcattta tcccgacgaa aagcgcttta ctcctggcga 65400 gcagatggaa tagactctgc tcatcaacta aagagggtga cgaaatggcg agtatcaccg 65460 tatggattgc tactgcttta ctttgcactg gagacggctg cgtccagatg ccggaccata 65520 ctagcagacg gttcgacagt aaggctcagt gcgaagacgt catgctgaga gcgattgata 65580 agatgtggga gcggcaccaa ttggtcgtcc aggccgtttg cacgccttat ttcctgagta 65640 gcactgagac gcccggattc tacagtccgc cgccccatcc accgactggt ctgaaccaca 65700 tgtgggacaa ctgggttcgc ggcggcagtc taccatccta tgaaccggga agagggtgga 65760 gcgaatgaag ccgcgccgtc cggaagttcg ggtgagcctg gaaaccgccc tctggatgtc 65820 gacatccgct gcactcctcg cggcgattat cgccggcgcg gttttccctt cttcgacgat 65880 tcaatgtccg gaagaaagac cgcctgcggc cgagcgcttc caccatcctg aaaacagcaa 65940 attctttcct cacatacaaa agggatagtg agtatgaagt atgtagtcct gaagatgacg 66000 gtccgtggca tgtcgcgtga agttcctgtg atcttccccg acctcataag tcatgcgaac 66060 atggccgcga gtgcgattgt ggcccttgat gctgagtgcg aaggtttcaa gaaggccggc 66120 gacaaagttg atatcgtcgc agcatcggca ggattcctgt cttcgatgga tatcgatgcg 66180 aaatgctacg gccagtcgga ctctttgggc ggtctgaagt cgagagaatc agaggatggt 66240 gaactcatcc gaatgatcga ctatacccat ggttacgtcg gttaaggcgc gctgcctttc 66300 ctgcgacaga cgcgccgtcc tggacgaacg aaaactaaag tcgaagcgac cgccaatttg 66360 tagatggtgt ggaggatcga cctggcgaat agtcatggaa gttacctgtt atagttcgtg 66420 taggccctat ccccacaggg ctggctcggt cggatgcatt ctagaccgat caggctcaac 66480 aacaa 66485

Claims (10)

녹농균에 특이적인 사멸능을 갖는, 서열번호 1로 표시되는 염기서열로 이루어진 박테리오파지 PA4.
Bacteriophage PA4 consisting of the nucleotide sequence shown in SEQ ID NO: 1, which has a killing activity specific to P. aeruginosa.
제1항에 있어서, 상기 박테리오파지는 수탁번호 KFCC11697P인, 박테리오파지 PA4.
2. The bacteriophage according to claim 1, wherein said bacteriophage is deposited under accession number KFCC11697P.
제1항에 있어서, 상기 녹농균은 항생제 내성 녹농균인 것인, 박테리오파지 PA4.
The bacteriophage PA4 according to claim 1, wherein the Pseudomonas aeruginosa is an antibiotic resistant P. aeruginosa.
제3항에 있어서, 상기 항생제는 카르바페넴계 항생제인 것인, 박테리오파지 PA4.
4. The bacteriophage PA4 according to claim 3, wherein the antibiotic is a carbapenem antibiotic.
제1항의 박테리오파지 PA4를 포함하는, 항생용 조성물.
An antibiotic composition comprising the bacteriophage PA4 of claim 1.
제1항의 박테리오파지 PA4를 포함하는, 사료 첨가용 조성물.
A composition for feed addition comprising the bacteriophage PA4 of claim 1.
제6항의 사료 첨가용 조성물을 포함하는, 사료.
A feed comprising the feed additive composition of claim 6.
제1항의 박테리오파지 PA4를 포함하는, 소독제.
A disinfectant comprising bacteriophage PA4 of claim 1.
제1항의 박테리오파지 PA4를 포함하는, 세척제.
A cleaning agent comprising the bacteriophage PA4 of claim 1.
제1항의 박테리오파지 PA4를 인간을 제외한 개체에 투여하는 단계를 포함하는, 녹농균에 의한 감염성 질병의 예방 또는 치료 방법.A method for preventing or treating an infectious disease caused by P. aeruginosa, comprising the step of administering the bacteriophage PA4 of claim 1 to an individual other than a human.
KR1020170176309A 2016-12-22 2017-12-20 Novel Pseudomonas aeruginosa specific bacteriophage PA4 and antibacterial composition comprising the same KR20180073489A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112522214A (en) * 2020-12-30 2021-03-19 瑞科盟(青岛)生物工程有限公司 High-lytic pseudomonas aeruginosa bacteriophage RDP-PA-20001 and application thereof
WO2023063453A1 (en) * 2021-10-14 2023-04-20 주식회사 마이크로바이오틱스 Bacteriophage specific to pseudomonas having antibiotic resistance

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112522214A (en) * 2020-12-30 2021-03-19 瑞科盟(青岛)生物工程有限公司 High-lytic pseudomonas aeruginosa bacteriophage RDP-PA-20001 and application thereof
WO2023063453A1 (en) * 2021-10-14 2023-04-20 주식회사 마이크로바이오틱스 Bacteriophage specific to pseudomonas having antibiotic resistance

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