KR102093241B1 - Novel bacteriophage having pathogen Salmonella Entritidis―specific antibacterial activity and use thereof - Google Patents

Novel bacteriophage having pathogen Salmonella Entritidis―specific antibacterial activity and use thereof Download PDF

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KR102093241B1
KR102093241B1 KR1020180110221A KR20180110221A KR102093241B1 KR 102093241 B1 KR102093241 B1 KR 102093241B1 KR 1020180110221 A KR1020180110221 A KR 1020180110221A KR 20180110221 A KR20180110221 A KR 20180110221A KR 102093241 B1 KR102093241 B1 KR 102093241B1
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박미경
이민정
송원근
최인영
이화은
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Abstract

본 발명은 병원성 살모넬라 엔테리티디스균 특이적인 사멸능을 나타내는 신규 박테리오파지 및 이를 포함하는 항균 조성물에 관한 것이다. 또한 본 발명은 상기 박테리오파지 또는 상기 항균 조성물을 이용하여 감염성 질병 예방용 조성물, 항생제, 소독제 등 다양하게 활용하는 방법에 관한 것이다.The present invention relates to a novel bacteriophage showing the specific killing ability of pathogenic Salmonella enteritidis bacteria and an antibacterial composition comprising the same. In addition, the present invention relates to a method for variously utilizing a composition for preventing infectious diseases, antibiotics, and disinfectants using the bacteriophage or the antibacterial composition.

Description

살모넬라 엔테리티디스균의 증식을 억제하는 신규 박테리오파지 및 이의 용도{Novel bacteriophage having pathogen Salmonella Entritidis―specific antibacterial activity and use thereof}Novel bacteriophage having pathogen Salmonella Entritidis―specific antibacterial activity and use thereof}

본 발명은 새롭게 분리 및 동정된 신규 박테리오파지 및 이를 유효성분으로 포함하는 병원성 살모넬라 엔테리티디스균(Salmonella Entritidis)의 증식 억제 또는 사멸용 조성물, 병원성 살모넬라 엔테리티디스균 감염성 질병 예방용 조성물, 항생제, 소독제에 관한 것이다.The present invention newly isolated and identified a novel bacteriophage and this pathogenic Salmonella Entebbe utility discharge bacteria composition for growth inhibition or death (Salmonella Entritidis) comprising as an active ingredient, the pathogenic Salmonella Entebbe utility discharge bacteria infectious prophylactic compositions, antibiotics, antiseptics for It is about.

살모넬라(Salmonella)는 일정한 유사 성향을 가지고 있는 군의 세균류에 붙여진 속명으로서 이 명칭은 1885년에 D. E. Salmon이 그의 공동연구자 Theobald Smith와 같이 돼지 Cholera bacillus를 발견한 것을 기념하여 이와 유사한 세균에 대해 일괄적으로 명명한 것이다. Salmonella (Salmonella) are collectively about to celebrate a discovery pigs Cholera bacillus similar bacteria, such as the name of the researcher is DE Salmon his collaborators in 1885 Theobald Smith as a generic name given to a group bacteria have certain similar tendencies It is named.

살모넬라균 중 살모넬라 엔테리티디스균은 살모넬라 속의 돼지 콜레라균으로 잘 알려진 균으로서, 사람과 동물 모두에게 감염되는 균이다. 돼지 콜레라의 잠복기는 평균 6~8일이며 40~41℃의 체열과 식욕부진, 결막염, 변비, 황회색 설사, 구토, 후구 마비 및 경련 등의 증상을 나타낸다. 가금류, 달걀, 육류, 유제품과 같은 동물 기원 식품은 일반적으로 살모넬라균의 매개체로 인식되고 있으며, 살모넬라의 감염을 줄이기 위해 USDA의 Food Safety and Inspection service는 가금류와 육류 설비를 현대화하기 위한 새로운 요구사항을 확립시켰다(1996). 다음과 같은 노력이 살모넬라균 오염의 가능성을 낮추었으나, 완전히 제거하지 못하여 화학물질, 약품, 또는 다른 대체물과 같은 항균물질이 소개되었다. 그러나 항균제의 지속적인 사용은 식품에 항생제 잔류물과 다제 내성 살모넬라균의 출현과 같은 부정적인 영향을 초래하였다. 또한, 매년 대략 15만 명이 살모넬라균에 감염되고, 모든 식중독균 중 가장 높은 비율로 치사되고 있어 치료하는데 36억 원 이상이 소비된다(2014).Among Salmonella, Salmonella enteritidis is a bacterium that is well known as a porcine cholera bacteria of the genus Salmonella, and is a bacterium that infects both humans and animals. The incubation period of swine cholera is on average 6 to 8 days and shows symptoms such as fever, loss of appetite, conjunctivitis, constipation, yellowish-white diarrhea, vomiting, posterior paralysis and convulsions. Foods of animal origin, such as poultry, eggs, meat, and dairy products, are generally recognized as carriers of Salmonella, and to reduce Salmonella infection, USDA's Food Safety and Inspection service sets new requirements for modernizing poultry and meat facilities. Was established (1996). The following efforts have reduced the likelihood of Salmonella contamination, but have not been completely eliminated, leading to the introduction of antibacterial substances such as chemicals, drugs, or other substitutes. However, continued use of antimicrobial agents has led to negative effects such as the appearance of antibiotic residues and multidrug resistant Salmonella in food. In addition, approximately 150,000 people are infected with Salmonella every year and are killed at the highest rate among all food poisoning bacteria, which consumes more than 3.6 billion won to treat (2014).

따라서 살모넬라 엔테리티디스균의 감염을 방지할 수 있고 또한 감염을 억제하기 위하여 친환경적인 방식이 요구되고 있으며, 이러한 연구 중 하나가 자연계 환경 도처에 존재하면서 특정 세균만을 죽이는 바이러스인 박테리오파지를 활용하는 것이다. 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 사멸시킨다. 박테리오파지는 매우 특이성이 높아서 특정 박테리아만을 사멸시키고, 온도, pH, 유기용매에서 비교적 안정한 장점이 있으므로 항생제 대체제 및 병원성 세균을 제어할 수 있는 biocontrol agent 및 bio-recognition agent로서 각광받고 있다.Therefore, it is possible to prevent the infection of Salmonella enteritidis and an eco-friendly method to suppress the infection, and one of these studies is to utilize bacteriophage, a virus that kills only specific bacteria while being present in the natural environment. Bacterial phage proliferates inside bacterial cells after infection, and after proliferation, bacteria are killed by destroying the cell wall of the host bacteria when the progeny bacteriophage comes out of the bacteria. Since bacteriophage is highly specific, it kills only specific bacteria and has relatively stable advantages in temperature, pH, and organic solvents, so it is spotlighted as a biocontrol agent and bio-recognition agent that can control antibiotics and pathogenic bacteria.

이에 따라 항생제에 비하여 숙주 특이성이 높은 박테리오파지에 대한 관심이 높아짐에 따라 살모넬라 엔테리티디스에 특이적인 용균활성을 갖는 박테리오파지 및 이의 응용에 대한 기술 개발이 필요하다.Accordingly, as interest in bacteriophage having higher host specificity than antibiotics increases, it is necessary to develop a technology for bacteriophage having a specific lytic activity to Salmonella enterididis and its application.

대한민국 등록특허 (0001) KR 10-1260655Republic of Korea Registered Patent (0001) KR 10-1260655

이에, 본 발명자들은 항생제의 오남용으로 인한 항생제 내성균의 문제점 및 식품 내의 항생제의 잔류 문제 및 과거 항생제와 같이 광범위한 숙주범위의 문제점을 해결하기 위해, 병원성 살모넬라 엔테리티디스균(Salmonella Enteritidis)을 사멸시킬 수 있는 신규 박테리오파지를 자연계에서 분리하였으며, 신규 박테리오파지 KFS-SE2(KCTC 13464BP)의 형태학적, 생화학적 및 유전적 특성을 검토하였다. Accordingly, the present inventors can kill the pathogenic Salmonella Enteritidis, to solve the problem of antibiotic-resistant bacteria caused by misuse of antibiotics, the problem of residual antibiotics in food, and a wide range of host ranges, such as past antibiotics. The new bacteriophage was isolated from nature, and the morphological, biochemical and genetic properties of the new bacteriophage KFS-SE2 (KCTC 13464BP) were examined.

본 발명의 목적은 병원성 살모넬라 엔테리티디스균을 특이적으로 사멸시킬 수 있는 능력을 갖는 박테리오파지 KFS-SE2(KCTC 13464BP)를 제공하는 것이다. An object of the present invention is a bacteriophage having the ability to specifically kill pathogenic Salmonella enteritidis. It is to provide KFS-SE2 (KCTC 13464BP).

본 발명의 다른 목적은 병원성 살모넬라 엔테리티디스균에 감염하여 병원성 살모넬라 엔테리티디스균을 사멸시킬 수 있는 박테리오파지 KFS-SE2(KCTC 13464BP)를 유효성분으로 포함하는 병원성 살모넬라 엔테리티디스균의 감염을 방지하는 데에 활용 가능한 조성물 및 이 조성물을 이용한 병원성 살모넬라 엔테리티디스균의 감염 방지 방법을 제공하는 것이다.Another object of the present invention is to prevent the infection of pathogenic Salmonella enteritidis bacteria, which contains the bacteriophage KFS-SE2 (KCTC 13464BP), which can kill the pathogenic Salmonella enteritidis bacteria by infecting the pathogenic Salmonella enteritidis. It is to provide a composition that can be used to and a method for preventing infection of pathogenic Salmonella enteritidis using the composition.

본 발명의 또 다른 목적은 박테리오파지 KFS-SE2(KCTC 13464BP)를 유효성분으로 포함하는 항생제, 소독제 또는 세척제를 제공하는 것이다. Another object of the present invention is bacteriophage It is to provide an antibiotic, disinfectant or detergent containing KFS-SE2 (KCTC 13464BP) as an active ingredient.

상기 목적을 달성하기 위하여, 본 발명은 병원성 살모넬라 엔테리티디스균을 특이적으로 사멸시킬 수 있는 능력을 갖는 박테리오파지 KFS-SE2(KCTC 13464BP)를 제공한다. In order to achieve the above object, the present invention is a bacteriophage having the ability to specifically kill pathogenic Salmonella enteritidis. Provides KFS-SE2 (KCTC 13464BP).

또한, 본 발명은 박테리오파지 KFS-SE2(KCTC 13464BP)를 유효성분으로 포함하는 항생제를 제공한다. In addition, the present invention is a bacteriophage It provides an antibiotic containing KFS-SE2 (KCTC 13464BP) as an active ingredient.

또한, 본 발명은 박테리오파지 KFS-SE2(KCTC 13464BP)를 유효성분으로 포함하는 소독제 또는 세척제를 제공한다.In addition, the present invention is a bacteriophage It provides a disinfectant or detergent containing KFS-SE2 (KCTC 13464BP) as an active ingredient.

삭제delete

본 발명의 박테리오파지는 병원성 살모넬라 엔테리티디스균의 감염에 따른 질병의 예방에 유용하게 이용할 수 있을 것이다. The bacteriophage of the present invention may be useful for the prevention of diseases caused by infection of pathogenic Salmonella enteritidis bacteria.

도 1은 병원성 살모넬라 엔테리티디스균 ATCC 13076에 대한 박테리오파지 KFS-SE2(KCTC 13464BP)의 용균 활성을 나타낸 것이다.
도 2는 신규 박테리오파지 KFS-SE2의 투과전자 현미경 사진이다.
도 3은 신규 박테리오파지 KFS-SE2의 온도 안정성 실험 결과를 나타낸 것이다.
도 4는 신규 박테리오파지 KFS-SE2의 pH 안정성 실험 결과를 나타낸 것이다.
도 5는 신규 박테리오파지 KFS-SE2의 유기용매 안정성 실험 결과를 나타낸 것이다.
도 6은 신규 박테리오파지 KFS-SE2의 SDS-PAGE 결과를 나타낸 것이다.
도 7은 신규 박테리오파지 KFS-SE2의 전기영동 결과를 나타낸 것이다.
도 8은 신규 박테리오파지 KFS-SE2의 시험분석(Challenge assay) 결과를 나타낸 것이다.
도 9는 신규 박테리오파지 KFS-SE2의 저장성 실험 결과를 나타낸 것이다.
Figure 1 shows the lytic activity of the bacteriophage KFS-SE2 (KCTC 13464BP) against pathogenic Salmonella enteritidis bacteria ATCC 13076.
2 is a transmission electron micrograph of a novel bacteriophage KFS-SE2.
Figure 3 shows the results of the temperature stability experiment of the new bacteriophage KFS-SE2.
Figure 4 shows the results of the pH stability experiment of the new bacteriophage KFS-SE2.
Figure 5 shows the results of the organic solvent stability experiment of the new bacteriophage KFS-SE2.
Figure 6 shows the SDS-PAGE results of the novel bacteriophage KFS-SE2.
7 shows the results of electrophoresis of the new bacteriophage KFS-SE2.
Figure 8 shows the results of the test assay (Challenge assay) of the new bacteriophage KFS-SE2.
Figure 9 shows the storage results of the novel bacteriophage KFS-SE2.

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

본 발명은 병원성 살모넬라 엔테리티디스균을 특이적으로 사멸시킬 수 있는 능력을 갖는 박테리오파지 KFS-SE2(KCTC 13464BP), 및 이를 유효성분으로 포함하는 조성물을 이용하는 병원성 살모넬라 엔테리티디스균의 감염 방지 및 병원성 살모넬라 엔테리티디스균에 의해 유발되는 질환에 대한 예방 및 치료방법을 제공한다.The present invention prevents infection and pathogenicity of the pathogenic Salmonella enteritidis bacteria using a bacteriophage KFS-SE2 (KCTC 13464BP) having the ability to specifically kill the pathogenic Salmonella enteritidis, and a composition comprising the same as an active ingredient Provides a method for preventing and treating diseases caused by Salmonella enteritidis.

본 발명의 박테리오파지 KFS-SE2는 본 발명자들에 의해 분리된 후 2018년 01월 22일자로 한국생명공학원구원 생물자원센터에 기탁되었다.The bacteriophage KFS-SE2 of the present invention was deposited by the inventors and deposited with the Korea Institute of Bioscience and Biotechnology Biological Resource Center on January 22, 2018.

본 발명에서 용어 "박테리오파지(bacteriophage)"는 특정 세균에 감염하여 당해 세균의 성장을 억제하고 저해하는 세균 특이적 바이러스로, 단일 혹은 이중 사슬의 DNA(Deoxyribonucleic acid) 또는 RNA(Ribonucleic acid)를 유전 물질로 포함하는 바이러스를 의미한다.In the present invention, the term "bacteriophage (bacteriophage)" is a bacteria-specific virus that inhibits and inhibits the growth of the bacteria by infecting a specific bacteria, single or double chain DNA (Deoxyribonucleic acid) or RNA (Ribonucleic acid) genetic material It means the virus containing.

본 명세서에서 사용된 "방지" 또는 "예방"라는 용어는 (ⅰ) 병원성 살모넬라 엔테리티디스균 감염의 방지; 및 (ⅱ) 병원성 살모넬라 엔테리티디스균 감염에 의한 질병으로의 발전을 억제하는 것을 의미한다.The term "prevention" or "prevention" as used herein includes (i) prevention of pathogenic Salmonella enteritidis infection; And (ii) inhibiting the development of pathogenic Salmonella enteritidis infection.

본 명세서에서 사용된 "치료"라는 용어는 (ⅰ) 병원성 살모넬라 엔테리티디스균에 의해 유발된 질환의 억제; 및 (ⅱ)병원성 살모넬라 엔테리티디스균에 의해 유발된 질환의 병적 상태를 경감시키는 모든 행위를 의미한다.As used herein, the term "treatment" includes (i) inhibition of disease caused by pathogenic Salmonella enteritidis; And (ii) all actions that alleviate the pathological condition of the disease caused by the pathogenic Salmonella enteritidis.

본 명세서의 "분리", "분리한" 또는 "분리된"은 자연 상태로부터 여러 실험 기법을 활용하여 박테리오파지를 분리하는 것과 타 박테리오파지와 구별하여 특정 지을 수 있는 특징을 확보하는 일을 지칭하며, 이에 더하여 생물공학기술로 박테리오파지를 산업적으로 활용할 수 있게끔 증식시키는 것도 포함한다."Separation", "separated" or "separated" in the present specification refers to separating a bacteriophage by using various experimental techniques from a natural state and securing characteristics that can be distinguished from other bacteriophage. In addition, it includes proliferation of bacteriophage for industrial use by biotechnology.

본 발명의 명세서에 있어서, 상기 ‘KFS-EC2’에는 박테리오파지 자체뿐만 아니라 박테리오파지 배양물도 포함된다.In the specification of the present invention, the 'KFS-EC2' includes not only the bacteriophage itself but also the bacteriophage culture.

본 발명에 따른 KFS-EC2는 통상적인 박테리오파지 배양법에 의해 대량으로 배양할 수 있다. 배양 배지로는 탄소원, 질소원, 비타민 및 미네랄로 구성된 배지를 사용할 수 있다. 예를 들어, TSB(tryptic soy broth), LB(luria-bertani broth) 와 같은 액체 배지, 또는 TSA(tryptic soy agar) 와 같은 고체배지 등을 사용할 수 있다. 배양은 통상의 배양조건으로 수행할 수 있다. 배양액 중의 배양배지를 제거하고 농축된 균체만을 회수하기 위해 원심분리 또는 여과과정을 거칠 수 있으며 이러한 단계는 당해 기술 분야에서 통상의 지식을 가진 자의 필요에 따라 수행할 수 있다. 농축된 균체는 통상적인 방법에 따라 냉동하거나 냉동 건조하여 그 활성을 잃지 않도록 보존할 수 있다. KFS-EC2 according to the present invention can be cultured in large quantities by a conventional bacteriophage culture method. As the culture medium, a medium composed of a carbon source, a nitrogen source, vitamins and minerals can be used. For example, a liquid medium such as tryptic soy broth (TSB), luria-bertani broth (LB), or a solid medium such as tryptic soy agar (TSA) may be used. Cultivation can be performed under normal culture conditions. In order to remove the culture medium in the culture medium and recover only the concentrated cells, centrifugation or filtration can be performed, and these steps can be performed according to the needs of those skilled in the art. The concentrated cells may be frozen or freeze-dried according to a conventional method to preserve their activity.

본 발명의 조성물에 포함되는 약제학적으로 허용되는 담체는 제제 시에 통상적으로 이용되는 것으로서, 락토오스, 덱스트로오스, 수크로오스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산칼슘, 알지네이트, 젤라틴, 규산칼슘, 미세결정성 셀룰로오스, 폴리비닐피롤리돈, 셀룰로오스, 물, 시럽, 메틸 셀룰로오스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은아니다. 본 발명의 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다.The pharmaceutically acceptable carrier included in the composition of the present invention is commonly used in formulation, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, Microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, but is not limited thereto . The composition of the present invention may further include a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components.

본 발명의 조성물은 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화 됨으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수도 있다. 이때 제형은 오일 또는 수성 매질 중의 용액, 현탁액 또는 유화액 형태이거나 엑스제, 분말제, 과립제, 정제 또는 캡슐제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수도 있다.The composition of the present invention is prepared in a unit dose form by being formulated using a pharmaceutically acceptable carrier and / or excipient according to a method that can be easily carried out by those skilled in the art to which the present invention pertains, or It can also be manufactured by incorporating it into a multi-dose container. At this time, the formulation may be in the form of a solution, suspension, or emulsion in an oil or aqueous medium, or may be in the form of ex-agent, powder, granule, tablet or capsule, or may further include a dispersant or stabilizer.

본 발명의 조성물은 활용 방식에 따라, 이에 국한되지 않지만 소독제, 음수첨가제 및 사료첨가제로 구현될 수 있다.The composition of the present invention may be embodied as a disinfectant, a negative additive, and a feed additive, but is not limited thereto, depending on the method of use.

본 발명의 박테리오파지 KFS-SE2는 병원성 살모넬라 엔테리티디스균을 특이적으로 사멸시킬 수 있는 박테리오파지로서, 정이십면체형 껍질(icosahedral capsid)을 가지며 꼬리 (tail)가 관찰되는 구조 (도 2)를 갖는, 형태학상 시포비리대(Siphoviridae)에 속하는 박테리오파지이다. 박테리오파지 KFS-SE2의 DNA 사이즈는 대략 47-48 kbp로 확인되었다(도 7). 박테리오파지 KFS-SE2의 pH 안정성에 있어서는 pH 2.0부터 pH 12.0까지 활성을 잃지 않고 안정적이었으며(도 4), 온도 안정성에 있어서는 4 ~ 50℃에서 1시간 동안 노출시 활성을 잃지 않고 유지하였다(도 3). 유기용매인 아이소프로판올(isopropanol) 및 에탄올(ethanol)에서 용균활성을 유지하였으며(도 5), 세척제인 25% 클로로폼(chloroform), 10% 클로로폼(chloroform), 0.1% 시트르산(citric acid), 1% 시트르산(citric acid), 0.1% 과산화아세트산(peracetic acid), 1% 과산화아세트산(peracetic acid), 100ppm 차아염소산나트륨(sodium hypochlorite), 200ppm 차아염소산나트륨(sodium hypochlorite)에서 용균활성이 감소하였다(도 5). 챌린지어세이 결과, 박테리오파지 KFS-SE2의 용균활성은 MOI 100에서 0-2시간 배양하는 동안 유의적으로 차이가 있었다(도 8). 박테리오파지 KFS-SE2 저장성 시험 결과, -20, 4, 22℃에서는 안정하였으며, -80℃에서는 저장 2주 후부터 활성이 감소하는 것으로 나타났다(도 9). The bacteriophage KFS-SE2 of the present invention is a bacteriophage capable of specifically killing pathogenic Salmonella enteritidis, having an icosahedral capsid and having a structure in which a tail is observed (FIG. 2). It is a bacteriophage belonging to Siphoviridae morphologically. The DNA size of the bacteriophage KFS-SE2 was confirmed to be approximately 47-48 kbp (FIG. 7). In the pH stability of the bacteriophage KFS-SE2, it was stable without losing activity from pH 2.0 to pH 12.0 (FIG. 4), and in temperature stability, it was maintained without losing activity when exposed at 4-50 ° C. for 1 hour (FIG. 3). . The lytic activity was maintained in the organic solvents isopropanol and ethanol (FIG. 5), 25% chloroform, 10% chloroform, 0.1% citric acid, The lytic activity was reduced in 1% citric acid, 0.1% peracetic acid, 1% peracetic acid, 100 ppm sodium hypochlorite, and 200 ppm sodium hypochlorite ( Fig. 5). As a result of the challenge assay, the lytic activity of the bacteriophage KFS-SE2 was significantly different during incubation for 0-2 hours in MOI 100 (FIG. 8). As a result of the bacteriophage KFS-SE2 storage test, it was stable at -20, 4, and 22 ° C, and at -80 ° C, activity decreased after 2 weeks of storage (FIG. 9).

이하, 본 발명에 대하여 보다 상세히 설명한다. 본 명세서에 기재되지 않은 내용은 당해 기술 분야 또는 유사 분야에서 숙련된 자이면 충분히 인식하고 유추할 수 있는 것이므로 그 설명을 생략한다.Hereinafter, the present invention will be described in more detail. The contents not described in this specification can be sufficiently recognized and inferred by those skilled in the art or similar fields, and the description thereof will be omitted.

<실시예 1> 병원성 살모넬라 엔테리티디스균에 감염하는 박테리오파지의 분리<Example 1> Isolation of bacteriophage infected with pathogenic Salmonella enteritidis

<1-1> 대상 박테리아 및 파지의 샘플링<1-1> Sampling of target bacteria and phage

경상남도 남강 소재 뱀장어 양식장의 도축 폐수 시료 25 mL을 시료액으로 준비하고, 이를 이용하여 소프트 아가 오버레이 (soft agar overlay) 방법을 수행하였다. 상기 소프트 아가 오버레이 방법이란 탑-아가 (top-agar, 0.4% 한천을 이용하여 고체 배지 위에 붙이는 것)에서 성장하는 숙주세포를 이용하여 박테리오파지가 용균하는 것을 관찰하는 방법이다.25 mL of slaughtered wastewater samples from an eel farm in Namgang, Gyeongsangnam-do, was prepared as a sample solution, and a soft agar overlay method was performed using the sample. The soft agar overlay method is a method of observing bacteriophage lysis using host cells growing in top-agar (top-agar, which is attached on a solid medium using 0.4% agar).

구체적으로, TSB 배지 225 mL에 샘플 25 mL와 병원성 살모넬라 엔테리티디스균(Salmonella Enteritidis ATCC 13076) 진탕 배양액 (OD640 = 0.3) 1%을 혼합하고 이를 37℃에서 160 rpm으로 16시간 동안 배양한 다음, 상기 배양액을 8,000 rpm에서 10분간 원심 분리하여 그 상등액을 0.25 ㎛ 필터로 여과하였다. 그 다음, TSA 평판 배지의 위에 TA soft agar [0.4%(w/v) agar, nutrient broth, NaCl, MgSO4, CaCl2] 4 mL와 병원성 살모넬라 엔테리티디스균 ATCC 13076 진탕 배양액 (OD640 = 0.3) 200 μl의 혼합액을 부어 굳힌 후, 그 위에 상기 시료액 10 μl를 첨가하고 37℃에서 16시간 동안 배양하여 용균반이 형성됨을 확인하였다.Specifically, 25% of the sample and 1% of pathogenic Salmonella Enteritidis ATCC 13076 shaking culture solution (OD 640 = 0.3) were mixed in 225 mL of TSB medium and incubated at 37 ° C for 160 hours at 160 rpm. , The culture solution was centrifuged at 8,000 rpm for 10 minutes, and the supernatant was filtered through a 0.25 μm filter. Then, 4 mL of TA soft agar [0.4% (w / v) agar, nutrient broth, NaCl, MgSO 4 , CaCl 2] on top of the TSA plate medium and pathogenic Salmonella enteritidis bacteria ATCC 13076 shaking culture (OD 640 = 0.3 ) 200 μl of the mixed solution was poured and hardened, 10 μl of the sample solution was added thereon, and cultured at 37 ° C. for 16 hours to confirm formation of a lysis plate.

상기 형성된 용균반으로부터 단일 박테리오파지를 분리하고자 하였다. 구체적으로, 상기 용균반을 900 μl의 SM 용액 (50 mM Tris-HCl, 100 mM NaCl, 10 mM MgSO4)을 첨가하고 실온에서 1시간 동안 볼텍싱하여 박테리오파지 용액을 수득하였다.It was intended to separate a single bacteriophage from the formed bacterial plaque. Specifically, 900 μl of SM solution (50 mM Tris-HCl, 100 mM NaCl, 10 mM MgSO 4 ) was added to the lysis plate and vortexed for 1 hour at room temperature to obtain a bacteriophage solution.

<1-2> 박테리오파지의 대량 배양 및 정제<1-2> Mass culture and purification of bacteriophage

상기 실시예 1-1에서 수득한 박테리오파지를 병원성 살모넬라 엔테리티디스균을 이용하여 대량으로 배양하고 이로부터 박테리오파지를 정제하였다.The bacteriophage obtained in Example 1-1 was cultured in large quantities using the pathogenic Salmonella enteritidis and the bacteriophage was purified therefrom.

구체적으로, 병원성 살모넬라 엔테리티디스균을 진탕배양하여 TA broth (nutrient broth, NaCl, MgSO4, CaCl2) 3 ㎖에 분주한 후, 2시간 배양시킨 후, 실시예 1-1에서 수득한 박테리오파지를 분주하여 마찬가지로 2시간 배양시킨 후, 원심분리하여 필터링하여 박테리오파지만을 분리하였다. 동일한 방법으로 TA broth의 양을 조절하여 8, 20, 200, 800 ml 순으로 진행한다. 그 다음 최종 농도가 10%(w/v)가 되도록 폴리에틸렌글리콜(polyethylene glycol, PEG)와 1M NaCl을 가하여 4℃에서 16시간 동안 추가 정치시켰으며, 4℃에서 8,000 rpm으로 20분간 원심 분리하여 침전물을 수득하였다. Specifically, the pathogenic Salmonella enteritidis was shake cultured and dispensed in 3 ml of TA broth (nutrient broth, NaCl, MgSO 4 , CaCl 2 ), cultured for 2 hours, and then the bacteriophage obtained in Example 1-1 After dispensing and incubating for 2 hours, the cells were centrifuged and filtered to isolate only bacteriophage. Adjust the amount of TA broth in the same way to proceed in the order of 8, 20, 200, 800 ml. Then, polyethylene glycol (PEG) and 1M NaCl were added so that the final concentration was 10% (w / v), which was further allowed to stand at 4 ° C. for 16 hours, and centrifuged at 4 ° C. at 8,000 rpm for 20 minutes to precipitate. Was obtained.

정제된 박테리오파지는 CsCl 밀도 구배 초고속 원심분리 (밀도 구배: 1.20, 1.30, 1.40, 1.45, 1.50, 1.70g/㎖) 4℃에서 22,000 rpm으로 2시간 동안 시행하였으며 SM 완충액 (50 mM Tris-HCl, 100 mM NaCl, 10 mM MgSO4)을 사용하여 투석 과정을 거친 후 4℃에서 보관하였다.The purified bacteriophage was subjected to CsCl density gradient ultrafast centrifugation (density gradient: 1.20, 1.30, 1.40, 1.45, 1.50, 1.70 g / ml) at 4 ° C for 2 hours at 22,000 rpm and SM buffer (50 mM Tris-HCl, 100 After passing through a dialysis process using mM NaCl, 10 mM MgSO 4 ), it was stored at 4 ° C.

본 발명자는 도축장으로부터 시료를 채취하여, 병원성 살모넬라 엔테리티디스균 ATCC 13076를 특이적 사멸시키는 상기 박테리오파지를 “KFS-SE2”로 명명하였다.The present inventor took a sample from a slaughterhouse and named the bacteriophage “KFS-SE2” that specifically kills pathogenic Salmonella enteritidis bacteria ATCC 13076.

<실시예 2> 분리된 박테리오파지 KFS-SE2의 특성 분석<Example 2> Characterization of isolated bacteriophage KFS-SE2

<2-1> 박테리오파지 KFS-SE2의 기타 병원성 균주 감염성 분석<2-1> Analysis of infectivity of other pathogenic strains of bacteriophage KFS-SE2

상기 실시예 1에서 정제한 박테리오파지 KFS-SE2가 살모넬라 엔테리티디스균 외의 병원성 균주를 대상으로 하여 감염 여부를 확인하기 위해 dot assay를 사용하여 숙주 저해능 범위를 확인하였다.In order to confirm whether the bacteriophage KFS-SE2 purified in Example 1 was infected with pathogenic strains other than Salmonella enteritidis, the range of host inhibitory activity was confirmed using dot assay.

구체적으로, 55종의 병원성 균을 각각 배양하여 각각의 배양액에 대해 상기 정제한 KFS-SE2의 용균반 형성 여부를 dot assay, 용균반검사(plaque assay)을 수행하여 확인하였다(도 1).Specifically, 55 pathogenic bacteria were cultivated, and whether or not the purified KFS-SE2 was formed for each culture medium was confirmed by performing dot assay and plaque assay (FIG. 1).

균주명Strain name 용균반
형성
여부
Lysis
formation
Whether
EOPs**EOPs ** 균주명Strain name 용균반
형성
여부
Lysis
formation
Whether
EOPsEOPs
SalmonellaEnteritidis ATCC 13076 SalmonellaEnteritidis ATCC 13076 ++ 1.001.00 Escherichia coli ATCC BAA-2192 Escherichia coli ATCC BAA-2192 -- -- Aeromonas hydrophila JUNAH Aeromonas hydrophila JUNAH -- -- Escherichia coli ATCC BAA-2196 Escherichia coli ATCC BAA-2196 -- -- Aeromonas hydrophila SNUFPC A10 Aeromonas hydrophila SNUFPC A10 -- -- Escherichia coli K12 ER 2738 Escherichia coli K12 ER 2738 -- -- Aeromonas hydrophila SNUFPC A3 Aeromonas hydrophila SNUFPC A3 -- -- Escherichia coli K12 VSM 1692 Escherichia coli K12 VSM 1692 -- -- Aeromonas hydrophila SNUFPC A5 Aeromonas hydrophila SNUFPC A5 -- -- Klebsiella pneumoniae ATCC 13883 Klebsiella pneumoniae ATCC 13883 -- -- Aeromonas hydrophila SNUFPC A7 Aeromonas hydrophila SNUFPC A7 -- -- Listeria innocua ATCC 33090 Listeria innocua ATCC 33090 -- -- Aeromonas hydrophila SNUFPC A9 Aeromonas hydrophila SNUFPC A9 -- -- Listeria monocytogenes 1911 Listeria monocytogenes 1911 -- -- Aeromonas hydrophila SNUFPC A11 Aeromonas hydrophila SNUFPC A11 -- -- Listeria monocytogenes G3982 4b Listeria monocytogenes G3982 4b -- Bacillus cereus ATCC 13061 Bacillus cereus ATCC 13061 -- -- Listeria monocytogenes G6055 Listeria monocytogenes G6055 -- -- Bacillus cereus ATCC 1611 Bacillus cereus ATCC 1611 -- -- Listeria monocytogenes H7738 Listeria monocytogenes H7738 -- -- Bacillus cereus ATCC 21768 Bacillus cereus ATCC 21768 -- -- Listeria monocytogenes H7757 Listeria monocytogenes H7757 -- -- Bacillus cereus NCCP 14795 Bacillus cereus NCCP 14795 -- -- Pseudomonas aeruginosa ATCC 9027 Pseudomonas aeruginosa ATCC 9027 -- -- Bacillus cereus RB002 Bacillus cereus RB002 -- -- Salmonella Dublin Salmonella Dublin Bacillus cereus RB003 Bacillus cereus RB003 -- -- Salmonella Hartford Salmonella Hartford -- -- Bacillus cereus RB005 Bacillus cereus RB005 -- -- Salmonella Heidelberg Salmonella Heidelberg -- -- Bacillus cereus RB011 Bacillus cereus RB011 -- -- Salmonella Mission Salmonella Mission -- -- Bacillus cereus RB013 Bacillus cereus RB013 -- -- Salmonella Montevideo Salmonella Montevideo -- -- Bacillus cereus RB015 Bacillus cereus RB015 -- -- Salmonella Newport Salmonella Newport -- -- Bacillus cereus RB020 Bacillus cereus RB020 -- -- Salmonella Panama Salmonella Panama -- -- Bacillus cereus RB037 Bacillus cereus RB037 -- -- Salmonella Salamae Salmonella Salamae -- -- Bacillus pumilus SR067 Bacillus pumilus SR067 -- -- Salmonella Senftenberg Salmonella Senftenberg -- -- Bacillus safensis SR138 Bacillus safensis SR138 -- -- Shigella boydii NCCP 11190 Shigella boydii NCCP 11190 -- -- Bacillus subtilis KACC 12680 Bacillus subtilis KACC 12680 -- -- Shigella flexneri 2457 Shigella flexneri 2457 -- -- Bacillus toyonensis SR070 Bacillus toyonensis SR070 -- -- Shigella sonnei ATCC 9290 Shigella sonnei ATCC 9290 -- -- Escherichia coli O157:H7 ATCC 43895 Escherichia coli O157: H7 ATCC 43895 -- -- Staphylococcus aureus ATCC 25923 Staphylococcus aureus ATCC 25923 -- -- Escherichia coli O157:H7 700599 Escherichia coli O157: H7 700599 -- -- Vibrio parahaemolyticus ATCC 17802 Vibrio parahaemolyticus ATCC 17802 -- -- Escherichia coli O157:H7 rifR Escherichia coli O157: H7 rifR -- -- Yersinia enterocolitica ATCC 23715 Yersinia enterocolitica ATCC 23715 -- -- Escherichia coli O157:H7 204p Escherichia coli O157: H7 204p -- --

<2-2> 온도에 따른 박테리오파지 KFS-SE2의 안정성 분석<2-2> Stability analysis of bacteriophage KFS-SE2 according to temperature

박테리오파지 KFS-SE2의 온도의 안정성을 확인하기 위하여 다양한 온도(-80℃, -20℃, 4℃, 22℃, 37℃, 50℃, 60℃ 및 70℃)에 노출 시킨 후 용균반검사를 진행하였다. After confirming the stability of the temperature of the bacteriophage KFS-SE2, it is exposed to various temperatures (-80 ℃, -20 ℃, 4 ℃, 22 ℃, 37 ℃, 50 ℃, 60 ℃ and 70 ℃) and then undergoes lysis test. Did.

구체적으로, 상기 각 온도의 1.30 × 108 PFU/mL 농도를 가진 KFS-SE2 1 mL를 1 시간 동안 상온에서 정치시킨 후 용균반검사를 이용하여 박테리오파지의 역가를 측정하였다.Specifically, 1 mL of KFS-SE2 having a concentration of 1.30 × 10 8 PFU / mL at each temperature was left at room temperature for 1 hour, and then the titer of the bacteriophage was measured using a lysis panel test.

그 결과, 박테리오파지 KFS-SE2는 70℃에서 용균활성이 소실되었으며, 4-50℃에서는 용균활성이 비교적 유지되는 것으로 나타났다(도 3).As a result, the bacteriophage KFS-SE2 showed that the lytic activity was lost at 70 ° C, and the lytic activity was relatively maintained at 4-50 ° C (FIG. 3).

<2-3> pH에 따른 박테리오파지 KFS-SE2의 안정성 분석<2-3> Stability analysis of bacteriophage KFS-SE2 according to pH

박테리오파지 KFS-SE2의 pH 안정성을 확인하기 위하여 다양한 pH(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 및 12)에 노출 시킨 후 용균반검사를 진행하였다. In order to confirm the pH stability of the bacteriophage KFS-SE2, after exposure to various pHs (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12), lysis test was performed.

구체적으로, 상기 각 pH 용액 900 μl와 3.52 × 108 PFU/mL 농도의 KFS-SE2 100 μl를 혼합하여 1시간 동안 상온에서 정치시킨 후 용균반검사를 이용하여 박테리오파지의 역가를 측정하였다.Specifically, 900 μl of each pH solution and 100 μl of KFS-SE2 at a concentration of 3.52 × 10 8 PFU / mL were mixed and allowed to stand at room temperature for 1 hour, and then the titer of the bacteriophage was measured using a lysis assay.

그 결과, 박테리오파지 KFS-SE2는 pH 3부터 pH 10까지 유의차가 없는 것으로 보아 넓은 범위의 pH에서 활성이 유지되는 것으로 나타났다(도 4).As a result, the bacteriophage KFS-SE2 was found to have no significant difference from pH 3 to pH 10, and thus, activity was maintained at a wide range of pH (FIG. 4).

<2-4> 유기용매에 따른 박테리오파지 KFS-SE2의 안정성 분석<2-4> Stability analysis of bacteriophage KFS-SE2 according to organic solvent

박테리오파지 KFS-SE2의 유기용매에 대한 안정성을 확인하기 위해 다양한 유기용매에 박테리오파지 KFS-SE2를 노출시켜 박테리오파지의 역가에 대한 안정성을 실험하였다. In order to confirm the stability of the bacteriophage KFS-SE2 to the organic solvent, the stability of the bacteriophage titer was tested by exposing the bacteriophage KFS-SE2 to various organic solvents.

구체적으로, 3.52 × 108 PFU/ml 농도의 KFS-SE2 용액 1 ml를 각각의 유기용매(chloroform, isopropanol 및 ethanol)에서 1시간 동안 정치시킨 다음, 용균반 검사로 역가를 측정하였다.Specifically, 1 ml of a KFS-SE2 solution having a concentration of 3.52 × 10 8 PFU / ml was left in each organic solvent (chloroform, isopropanol and ethanol) for 1 hour, and then titer was measured by lysis test.

그 결과, 박테리오파지 KFS-SE2는 아이소프로판올(isopropanol)과 에탄올(ethanol)에서 활성이 유지되었다(도 5). As a result, the activity of bacteriophage KFS-SE2 was maintained in isopropanol and ethanol (FIG. 5).

<2-5> 세척제에 따른 박테리오파지 KFS-SE2의 안정성 분석<2-5> Stability analysis of bacteriophage KFS-SE2 according to the cleaning agent

박테리오파지 KFS-SE2의 세척제의 종류와 농도에에 대한 안정성을 확인하기 위하여 박테리오파지 KFS-SE2를 노출시켜 안정성을 실험하였다. In order to confirm the stability to the type and concentration of the detergent of bacteriophage KFS-SE2, stability was tested by exposing bacteriophage KFS-SE2.

구체적으로, 3.52 × 108 PFU/ml 농도의 박테리오파지 KFS-SE2 용액 1 ml를 각각의 0.1% 시트르산(citric acid), 1% 시트르산(citric acid), 0.1% 과산화아세트산(peracetic acid), 1% 과산화아세트산(peracetic acid), 100 ppm 차아염소산나트륨(sodium hypochlorite), 200 ppm 차아염소산나트륨(sodium hypochlorite)에서 1시간 동안 반응시킨 후 용균반검사 방법으로 역가를 측정하였다.Specifically, 1 ml of a bacteriophage KFS-SE2 solution having a concentration of 3.52 × 10 8 PFU / ml was each 0.1% citric acid, 1% citric acid, 0.1% peracetic acid, and 1% peroxide. After reacting with acetic acid (peracetic acid), 100 ppm sodium hypochlorite, and 200 ppm sodium hypochlorite for 1 hour, the titer was measured by a lysis test method.

그 결과, 박테리오파지 KFS-SE2는 모든 농도의 세척제에서 용균활성이 감소하는 것으로 나타났다(도 5).As a result, the bacteriophage KFS-SE2 was found to decrease the lytic activity in all concentrations of detergent (Fig. 5).

<실시예 3> 박테리오파지 KFS-SE2의 전자현미경 분석<Example 3> Electron microscopy analysis of bacteriophage KFS-SE2

박테리오파지 KFS-SE2의 형태학적 분류를 위해 투과전자현미경(TEM) 관찰을 수행하였다. 박테리오파지 KFS-SE2를 copper TEM grid에 흡수시킨 후에, 2% phosphotungstic acid로 음성 염색하고 건조하였다. 상기 박테리오파지 KFS-SE2의 형태는 바이오-전자투과 현미경 H-7100 (Hitachi Ltd., Japan)를 이용해 100 kV의 전압으로 관찰하였다.For morphological classification of the bacteriophage KFS-SE2, transmission electron microscope (TEM) observation was performed. After the bacteriophage KFS-SE2 was absorbed into the copper TEM grid, it was negatively stained with 2% phosphotungstic acid and dried. The form of the bacteriophage KFS-SE2 was observed with a voltage of 100 kV using a bio-electron transmission microscope H-7100 (Hitachi Ltd., Japan).

그 결과, 박테리오파지 KFS-SE2 머리의 길이(length)와 너비(width)는 각각 65.44 ± 10.08 nm와 66.83 ± 8.51 nm로 확인되었고 박테리오파지 KFS-SE2 꼬리의 길이(length)와 너비(width)는 각각 135.21 ± 12.41 nm와 14.76 ± 2.03 nm였다. 시포비리대는 상대적으로 긴 꼬리와 비수축성 꼬리를 가진다. 따라서 박테리오파지 KFS-SE2 시포비리대(Siphoviridae)에 속하는 것으로 나타났다(도 2).As a result, the length and width of the bacteriophage KFS-SE2 head were found to be 65.44 ± 10.08 nm and 66.83 ± 8.51 nm, respectively, and the length and width of the bacteriophage KFS-SE2 tail were 135.21, respectively. ± 12.41 nm and 14.76 ± 2.03 nm. The sipoviridae has a relatively long tail and a non-shrinking tail. Therefore, it was found that the bacteriophage KFS-SE2 belongs to Siphoviridae (FIG. 2).

<실시예 4> 박테리오파지 KFS-SE2의 단백질 패턴 분석<Example 4> Protein pattern analysis of bacteriophage KFS-SE2

4.32×1011 PFU/mL 농도의 정제된 박테리오파지 KFS-SE2 용액 80 μl와 5x SDS 시료 용액 20 μl를 혼합하여 5분간 끓인 다음, 10% SDS-PAGE를 수행하였다. 80 μl of a purified bacteriophage KFS-SE2 solution at a concentration of 4.32 × 10 11 PFU / mL and 20 μl of a 5x SDS sample solution were mixed and boiled for 5 minutes, followed by 10% SDS-PAGE.

그 결과, 박테리오파지 KFS-SE2를 대상으로 수행한 SDS-PAGE 결과를 나타내는 전기영동 사진에서, 170 kDa에서 37 kDa 사이 범위에서 단백질 밴드가 확인되었다. 주요 밴드는 1가지이고 그 크기는 약 42 kDa로 확인할 수 있었다(도 6).As a result, in the electrophoresis photograph showing the SDS-PAGE results performed on the bacteriophage KFS-SE2, protein bands were identified in a range between 170 kDa and 37 kDa. The main band is one and the size was confirmed to be about 42 kDa (Fig. 6).

<실시예 5> 박테리오파지 KFS-SE2의 전체 유전자 분석<Example 5> Total gene analysis of bacteriophage KFS-SE2

박테리오파지 KFS-SE2의 전체 유전자를 분석하기 위해, 박테리오파지의 유전체를 Phage DNA Isolation Kit(NORGEN Ltd, Canada)를 사용하여 분리하였다. 분리된 박테리오파지의 전체 유전자 분석은 454 및 Illumina sequencing platforms의 혼합 방법과 CodonCode Aligner 3.7.1에 의하여 수행하였다. 전체 유전자의 크기를 전기영동으로 확인하였다.To analyze the entire gene of bacteriophage KFS-SE2, the genome of bacteriophage was isolated using Phage DNA Isolation Kit (NORGEN Ltd, Canada). Total gene analysis of the isolated bacteriophage was carried out by the mixing method of 454 and Illumina sequencing platforms and CodonCode Aligner 3.7.1. The size of the whole gene was confirmed by electrophoresis.

서열번호 1에 나타낸 바와 같이 박테리오파지 KFS-SE2의 전체 유전자 분석 결과, 이중가닥 DNA로 크기가 47.7 kbp이며, 전체 ORF 수는 84개임을 확인하였다. 박테리오파지 KFS-SE2의 전체 유전자 서열을 서열번호 1로 나타내었다(도 7).As shown in SEQ ID NO: 1, the whole gene analysis of the bacteriophage KFS-SE2 confirmed that the double-stranded DNA was 47.7 kbp in size and the total number of ORFs was 84. The entire gene sequence of bacteriophage KFS-SE2 is shown in SEQ ID NO: 1 (FIG. 7).

<실시예 6> 박테리오파지 KFS-SE2의 챌린지 어세이 분석<Example 6> Challenge assay analysis of bacteriophage KFS-SE2

병원성 살모넬라 엔테리티디스를 TSB 100 ml에 접종하고 190 rpm으로 37℃에서 3 시간 동안 배양시켰다. 배양액의 흡광도가 640 nm에서 약 0.3에 도달하면 (108 CFU/ml), 박테리오파지 KFS-SE2 현탁액 1 ml를 MOI 1, 100이 되도록 접종하여 37℃에서 110rpm으로 12 시간 동안 배양하여 파지의 세균 사멸능을 확인하였다. 박테리오파지 KFS-SE2를 첨가하지 않은 병원성 살모넬라 엔테리티디스 배양액을 대조군으로 사용하였다. 균 성장은 파장 640 nm에서의 흡광도를 측정하여 2 시간 간격으로 측정하였다. The pathogenic Salmonella enteritidis was inoculated into 100 ml of TSB and incubated at 190 rpm for 3 hours at 37 ° C. When the absorbance of the culture solution reaches about 0.3 at 640 nm (10 8 CFU / ml), 1 ml of the bacteriophage KFS-SE2 suspension is inoculated to be MOI 1, 100, and cultured at 37 ° C at 110 rpm for 12 hours to kill phage bacteria. Ability was confirmed. The pathogenic Salmonella enteritidis culture without addition of bacteriophage KFS-SE2 was used as a control. The growth of bacteria was measured at an interval of 2 hours by measuring absorbance at a wavelength of 640 nm.

그 결과, MOI 1에서는 박테리오파지 KFS-SE2가 세균 생장을 억제시키는 것으로 나타났으며, MOI 100에서는 박테리오파지 KFS-SE2가 0-4 시간 동안 세균 사멸시키는 것으로 나타났다(도 8).As a result, in MOI 1, bacteriophage KFS-SE2 was shown to inhibit bacterial growth, and in MOI 100, bacteriophage KFS-SE2 was shown to kill bacteria for 0-4 hours (FIG. 8).

<실시예 7> 박테리오파지 KFS-SE2의 저장성 분석<Example 7> Bacteriophage KFS-SE2 analysis of storage

박테리오파지 KFS-SE2(108 PFU/mL)의 저장성 분석을 위해 TA broth와 함께 다양한 온도 (-80℃, -20℃, 4℃ 및 22℃)에서 보관되었다. 동결 손상을 최소화하기 위해 글리세롤의 15%를 박테리오파지 KFS-SE2와 혼합하여 -80℃, -20℃에서 저장하였다. 2주 간격으로 -80℃, -20℃, 4℃ 및 22℃에 저장한 박테리오파지 KFS-SE2의 활성을 plaque assay 분석을 수행하여 확인하였다. Bacteriophage KFS-SE2 (10 8 PFU / mL) was stored at various temperatures (-80 ° C, -20 ° C, 4 ° C and 22 ° C) with TA broth for storage analysis. To minimize freezing damage, 15% of glycerol was mixed with bacteriophage KFS-SE2 and stored at -80 ° C and -20 ° C. The activity of bacteriophage KFS-SE2 stored at -80 ° C, -20 ° C, 4 ° C and 22 ° C at 2-week intervals was confirmed by performing a plaque assay analysis.

그 결과, 박테리오파지 KFS-SE2의 저장성은 -20, 4, 22℃에서는 안정하였으며, -80℃에서는 저장 2주 후부터 활성이 감소하는 것으로 나타났다(도 9). As a result, the storage capacity of the bacteriophage KFS-SE2 was stable at -20, 4, and 22 ° C, and at -80 ° C, the activity decreased after 2 weeks of storage (FIG. 9).

기탁기관명 : 한국생명공학연구원Depository name: Korea Research Institute of Bioscience and Biotechnology

수탁번호 : KCTC13464BPAccession number: KCTC13464BP

수탁일자 : 20180122Date of Deposit: 20180122

<110> KYUNGPOOK NATIONAL UNIVERSITY <120> Novel bacteriophage having pathogen Salmonella Entritidis specific antibacterial activity and use thereof <130> PN1712-479 <160> 1 <170> KoPatentIn 3.0 <210> 1 <211> 47399 <212> DNA <213> Unknown <220> <223> bacteriophage KFS-SE2 <400> 1 aaaaaaacaa gagcagggtc atgcttggtt attttgatga tttcttcgag gctgtatgtg 60 ccagaaagtc tgctgagata agcctcgaat ttcatagcaa tcacggcaaa taattacccg 120 taaactaccc ttaataacaa ttcgtgaaca ggcctcttct cttctgttaa catcatatcg 180 ccaagcggag attgcatctg tatgtagttc aggcagctat caatcgggtt ttcttttatg 240 tattcaatta tttcgttagc tttattatca acaacttcgg catcatattg cccttgctga 300 ccaacaacaa acagcttgaa ataaaagtca tttgataacc cttggcggat acctgttccg 360 ccacttgttt tcaggacaag aaagcgatcc tcgcctactc cagtatcatt ccataattga 420 agttgtgcag tccacccatc catcagtcct gcatcgttta aataattata aactcgctca 480 agcatattca tagtttcatc tccttcttaa tcacgccatc aacaaggtct ttggtgcgct 540 gcgccgcttt ggtcaggaat tgtgtctcac cgcccggcga ccagtatgtg ccattgccgt 600 tgctgcgtgg ccttcctttt agtttgccac tggcgttatg aacatacaga gcataattcg 660 cagaatagcc aaccttgcca gtgattcgcg ttccgttaac ttccacggta tcaaactgac 720 tgttaatcag cgttgatgta tcaattggcg ttagcgtggc tgattcggtg cggatgatgt 780 atgtcgctga cttgattgca cgcacagctt tcgtggcgat tatctcatcc acaatttgcg 840 aagttctctc tacagcctgc cggacacctc ttaatttcgc tggcattatg tcaccagtgc 900 aaagtctgga ggctctgccc tattgaaagt cgaaccgtaa ttaatcacac tcagaatctg 960 atttgcgcca gccgccagtg ggtcagcttc tgtcgccgtg ccaatcatga tgtagtcacc 1020 taccttagct gcagtgtatt ctgtccagaa ggtattcttc tgcacaatct cattaccttt 1080 cgcatcggtc gatacatcat cattaaagcc gtaatcacac atgatgctca ctggtgcatc 1140 aaaagtcggc ttgccgtact tgtcagtgcc gcttttgtgc cagatggtgc atggctgcgt 1200 gtaactccag ttagccagtg aagtcatttg catttactcc cacgcacaac cgcaaaccac 1260 ggttttccac ttccgtcagg gtcttcaacc aaatcaccag tgcatccagc tgtatccagt 1320 agcttcatct gattgtacag cgccacccac ggcttgcttc cgtaagcgaa tgattgtgat 1380 gcgccagacg gtgcgctctg gctggtgacg tagcgaccag ctgtatttgc gccaatcagg 1440 atggaggccc acagcatgat cgcattttgt cggcattcat cacttggata gttcagttca 1500 aggcattcac tgattgatgc tacaagacac agaataccgg acgcatccgt tgtggtgatg 1560 gtcatcccgc gcgatgccat ctggctgacc agttcttcag gtgttggtgc tgtcatttct 1620 ctttgactcc ctaactttcc accacatttc aaacaggttc tttattacca gagacagagc 1680 gccaagaatt gacgctactg ccgcccactc tgtcaggctg tgtggaatca tagcctcaaa 1740 ataagattgc gtgacaggtg tttgttctgc aactttcaga ccgataccgg tgccaataga 1800 agcgtatccg gccttgtcaa tcacctgtcc tgtcgttccg cttataatct gctctgcgac 1860 ttgccttagt gtcccgttca ttgcgtgtct cgctgatgat atgtttccag cacttataga 1920 tttgaatcag cgaaaaaaca atggcgacca cgccaagaat aatgtccaat ttcgccgccc 1980 catttaaaag tgatggaaag gatgaacaga tggatgccga taataataaa tgcgtactgc 2040 gcatgaagcg gcgtttctac aggcgtgata aattcccatg cgaatgactc tatcgctacc 2100 agccattcgt aaaggctcat cgtcagcacg cagagcgcca tctttgtact tttgcgcagc 2160 gcaatagccg gaaacaacca gaccatagac tgcgcaaggt aatacagata ttcggcggga 2220 aatgaatcaa caagcaccca tccaagatac acagacatca ccattgccgg aatgaacacc 2280 agaagcgcaa ccatgcctgt gcaggcaaac cccaacacat acatgatcat gatggcaatg 2340 tctgcgccga acattatttc ttgccgcgag atggtgagcg ggtggagccg tttggcttca 2400 ctgcgccagt tttggtattg ccagtagcgc gcgaacgaga aggtgaattg gtggaaccca 2460 tgtttaaatc ccctgttgtt tgattagcat gattttagca tattcctgtt gacgtagatt 2520 gatggtgcgt ttatagttag tgacgtagaa acaacaataa atgttagagg tgatgagatg 2580 tttgatattg ataacccaag tgatgacaaa gctaagctga ttgatgcagt cgcttgcagt 2640 tttgcttctt gccagacaga aggtgaatat caggttgtga aaatgtgcat tgttgagttc 2700 ttctcggcaa tcaacattcc tgacgatgag gctgttgata ttctgctgag ttccgctggc 2760 aattgcgctg atgcggacga atgcattgat gaactggttg aagagtttgg cggtattttt 2820 cagggtgacg aggagtgatt atgagcagta acgcaaaaca ttatgattat tacatggttg 2880 aaggtgctga tgttaagaat gttattgacg catatgatga catccaaaag cgccgcaatg 2940 aaattctcgg cgatgccatg aaaaaggttg gtgctgtcgc tttcactaca acacgtagct 3000 ggggcgcggt cggaggtggc ttacttgaga gctttgtgtg gagtgagcag tttgaatttc 3060 cgtgccaagt gacaataaag cgtgaagact tttgggaagg tcagcgtgta attgtggctc 3120 gcggaaaagg aaatacaaag gatgggcggg aatacaacaa aaagctggac gcagtgattc 3180 gcgaggcaaa cgagaaatta aagttattgc cagaatggaa ggactacatt gttaaccatt 3240 atggcattgc acgcacaggc attggcgagc aatcaggtcg cggatttggt tttgcaatgc 3300 tgtctactta tggcggtaaa cacccgcaaa aggatgattg cctgattttt gctgtgccaa 3360 atacaaaaga tgaaggtcac ggacaggtaa cgatacctga taactttaag cagataacat 3420 acggtcagtt ttacgatatt gctaattcag gtgatgagga ataaacaatg aaaacactaa 3480 gcaaaatcta ttcagacaaa gaaacacgca atggtatcgc ggttaacaaa acctatctcg 3540 tgccagttga gcaaatctat ctggagccgg ggtacaacat ccgtgaagca gatgagcagc 3600 acgtcgaata tttcgcgcag tgctgggaat ctggtcaacc attaccagca ttaacagtta 3660 ttcctgatga gaaaggcatt cgcattcttg atggtcagca ccgctatctc ggagcattgc 3720 gtgccattga gcgtggcgcg ccaatcgttc gcatcgagtg taaggatttc acgggcgatg 3780 aggcggataa aatcgcgttc atggtgtcat ccagtcaggg taagcaactt gacccgtttg 3840 aacgcgcaaa ggcttacacg cgactgaaag gctttggctg gacgaatgaa gaaatcgcca 3900 agaaggtagg tcgttcagta tctgacgtgc aaatgcattt gtcgcttggt gatgttccgg 3960 cggaagtaaa ggcgcgcatc agtgcaggac aaatcagcta tgcaaatgcc gtagcggtaa 4020 cgcgagaaca tggcgatgat gcggttaaag ttatcgacga agcggtcgaa gaagccaaag 4080 cacaaggcaa ggataaggtc acggcgaagg tgctgaagtc gaaaaagatt aagccagtag 4140 accgcctgat tgagttactg aagccagcgg accacgtaat tctccccgct ggtcatgtag 4200 tggcagagga tgaggagttc atccagattc ctgttgctga tattcatgag gtcatggcaa 4260 ttctggagaa gatgtgatga gtgaacagcc gcttgctttc agacaaatag aaagaaaagc 4320 tattaagagc cataaatgct gcgagtgtgg aagagaaata cacaaaggag ataaatataa 4380 gtattcatca ggaatctcat cggaaaaaga tgctttttcc tataaacaat gcttgatatg 4440 cagcaaggca ttcaatgcag catctgaaat ctcagattac gatgacatgc catgctttac 4500 gggtcttagg gagtggatgg gaaattactt ctctcgaaat taccctgcgc agaaaagcgt 4560 ggatagtata tgcatggact taggtttaac agaatcggaa gttcgataca tcattccagc 4620 taagtggttg gtcctatgaa cgctgaacaa ttcatcgaaa aacaacttcg caccaagcta 4680 cctgacattg accagatggc aattgatgcg gcaattcagt attacaagcg caatcagagc 4740 gcaaagaagg gtggcatttt tgaagaatgc ctgaaggttg caaaacagca tatgattaag 4800 gtgaagtgat gaaactaaaa atcagcaaat tattacttga gtcagcatta atatttcagg 4860 cgcgcaatga tgtgcgctac tacctgaatg gcatttgctt tatgcaagat ggtcgtgttt 4920 catcaactga cggtcatcgc gcattcattg gtggcagtca tgacaatacg ctgacagaaa 4980 atgtgattat caagattggc aaatctccaa caaaacgcta tgactacgcc atcattgata 5040 ccaagtcgaa aattgcaacg tatcatgatg aagctggcga gatggttggt gctggtatct 5100 gcgaagagat tgatggtcga ttccctgata ttgatcgcgt cattccgaag cagaccttac 5160 cagcagagga aattggattc aacgctggat atcttgttga tattgagaaa gtggcgaagc 5220 tgtttaatcc taaattctgc ggtgtcaaat ttgagcttaa tggaaataca aatgccgcag 5280 tttgctgtct tagtgcgcca tctggagata ctgcaaagat tgttgttatg cctatgcgcc 5340 tgtagcaata aaaagccccg tcatggggct tttcttttat tttgcatcca tggaagccac 5400 aataaaaaac ccgcattatg cgggttcagt ttactctgct ttctttttct ttatcgtctt 5460 ttcttgcggg gttgcgactt cgaaagactt ttccagctct ggcatgattc gcagttttgg 5520 tagcagatgc tcatctggtt cggtaatcac ctcgccaagc tgcaactcac gaatcttgcc 5580 tttctcttta acaaagattc cgcgtgcgat cacttcgtat ttagccatta ttcacctcaa 5640 attcacaaag gggccgaagc ccctatcttt attacttcgc aggttgcgtg ccgtatccgt 5700 tgaacacttt ggacttaccg gcgaaatcct tgcgcacctg taatcccata gctgaccaca 5760 ctaggaagtt gaagttatcg tgagggttta cgcgggccgc cgcataggtg gagacaggct 5820 gagcaacacg cggacggatg tacatatcgt tgcgaacgta gccaacgaaa tggttaccag 5880 tcagcaggaa gttggtgcca atctttccga tgcgaccgtt gccgaactgc gtgatgtact 5940 gctcaactgt gccgcctttg aagcccgccg cattagaata cggacgcatg aagctgcgac 6000 gcactgccgg ggaaacccac agagtcacct gctcaaatac gttctgcgca tccagaatag 6060 cctgaaaatc ctgattgaag aatttcacga tttcgtctgg cgttgcggtt tgcaggtcga 6120 tattcaggcc gcccccggaa acgttcaggt taacctgtac agtgttcggg tggttagtga 6180 taccgtaacc agtgtaaacg ccgttcacgt tcagagtctg gtcgccagtc agcaggtact 6240 gcgccatatc ggaacgcagg ttgaaggtga cgttagcctg atcgtccagc agtgggtcga 6300 aaccctcaga ctgcatgccc agcagttcgc gccattctcg gctgtagcca gtcttgaaga 6360 ttggaatcac atcgccagtg taatcgtagc gggttttatc caaatcttcc ggctcctgac 6420 cagacagagt gcgcacaacc ttaccagcat cggaagcaat gcgactgatt gccacggttt 6480 taccgatatt gatgtttgcc gcgataccca tcaggtcagc catcatgtcc tgaccagctt 6540 cgttacggaa aacgcgggta gtgacgttgt ccacgtcgcg ccagtaatct ttcgttacca 6600 gtgcggtggc gttcacaccg taagttttcg ccagctcagc ttctgcgttg cagaacacct 6660 tacggtcgat ggtcagatgt ttccactggt cagccactac tgcggagttg gctaccaggt 6720 ctttggtaaa aataatcttt tccattatta acctccagca ggcatgtaag cattgccagc 6780 gcgacgaact gcaaccagct cagcgccatc agaggcaaca gtataagttt cataggagta 6840 aaacaggata ttatccccat caccagcaac tttcagcgcg ccagcgccgt tgcttgccag 6900 cggagtgcct ttcttcagcg cagaagatgc agcaaccagt gcgtgatagg tgacgccaaa 6960 ttcacactgt acagccatgc cagtagcatt agccggaaca gcctcagaca catcgccacc 7020 accgaggtag ttatgctgaa gcacataagg gaaaccctga ccgccagcgg tagcgtgcgc 7080 gatgattttg tcgtcagcag tatcgaagtc aaccagtgcg cccggcttca acgcgacctt 7140 catgatgcct tcgcgaatct gcgggtcgtt cttgcgagct gggccaccaa tgatggtgcc 7200 ataacggata gtagccatta ttcaggtgcc tccatatcaa aatcgtcatc agcgtggttt 7260 ggctggaagc cacccttcag cgcggcaggc ttgctggtca gcgcataggt ttcacgcagt 7320 gcttcgcctt tcagcgcatt cacagcggat tccggcagtt ttagttcagc gatgatagca 7380 gcacgcatcg cggtttcttc ctgctcggtg ttcgcctgca attgctcttt cagtttaacg 7440 ttttcagctt cgatgtcggt cagcttctgg ttgacagctg tcaacgattc ctgaaccggc 7500 ttgagggctt cagcgagtac cgcctgtaat tcctcgttcg tcattgagat ttccccttca 7560 gttgatttta ccggctcaag ttcagtctta taaacagcct tgacccgctc accgaccaat 7620 tttaccacat catcttcaac gatgtagaac tgctgaaaaa tctggccttt gatttcgaat 7680 ccgacacggt cgtcgtacac agccacgata taaggccaga catcctcacc gacttcagcc 7740 ttcagaatct ggcgaatctg ttcgctgatg ttctcaaacg acaggtctga tttgttggtg 7800 atgtagttga tagccttatg tagccacgat ttataattaa tcttgttggc gctttcgtct 7860 ggcacggttg aatcctcaag gtttacggtg atgcgttcga tttgctcgcc attggtggca 7920 aagatgccaa caccatcttc tggcgttccg gctccctgca ctcccggtgg caggatggcg 7980 aggtggtccc attccatgtt gcgcgcaatc catgagtatt ttttgccttt gctcgtgcct 8040 tccgcagctt cgcggttgag caataagcca gttgatacat ggattggttc agcaccttca 8100 gctgagttca tcagcgactc aatgcgaccg agcaactcct gacctttctc tgagcgttca 8160 gcaataactt tgtttacttt aaggtcaaca agcaccttgc caccatcatg agaagcattc 8220 tctatccatg cgccaacatg atactggttt accgcccgaa tattgtgcgc agaaacgaaa 8280 gagccatcaa ccattgggtg gttgtatggt gctgggtttc catttagccc atgataacta 8340 ttgcgtatct cttccgccgg gtacaggccg ccgttcatca ctatgtcgtc gcatagaggg 8400 gtgacatttt ttataacgta gtgcaagtcg ccatcaatca cctgctcact gatattgctc 8460 gcggaattga tagtggtgag cacgttaact tgcaatctat tcatcgcgta gctccacggt 8520 tagttcgtgg tcgaattata acacagggag atatagcacc atgaggcggc agccagtgca 8580 aataatggcg aattggtgag tgcgtagaac gtgagaaaga aagtgatagg gattatgttc 8640 atgggctacc tcctgattaa atgatagtag cccatgatga acaaaaggta tacggagtta 8700 gtctgaaatc acatcatcca taaatgcgag cgcggcacat gaaaggcaga gcagggcgcc 8760 atagcaaatc atctggtaca gattgtccgc ctcaaacacc cttgcgaatg cgtaggctga 8820 taatatccac agtaatggaa tcatttacat accctcatta ttttgcgact atgaaatacg 8880 tgagatgaat cctctctaac tggcattgtc cccactggcg atttctcgca acgaatacac 8940 tttctagtcc aatatttttg gccagggtta aatctatacc aatcctttga ctcaccacac 9000 ctgtagcact gatacatgcg catcatacca acccagcctc ctgttttgcc cggtgaacgt 9060 atgacataaa cttgccaatc ggcatttcct tgcggatttg cgccagaatc gcgccatgca 9120 acatcctctc ctcgccaaaa tacagcttat cgagtcgcgt tttgatgagt gctcgcgtgc 9180 gcttcatatg gtcgcgtgcc ttaagtgctt tctcatgcca gacgcgatca ttcttcttat 9240 cggcatattg cagttgacgc tcaacggttt cgatttcaaa cgccagttgc atgtcataat 9300 cttcaagctg aatgatgtct gctttcataa tgtcgtttag ttggataatc attttttcac 9360 ctttaatcct gcttgtttga ttgcttcaat aacttcatct gcatagtaaa taacgtgaca 9420 tccaagactc tctacctctg gcaattcaat ctcaatagcc gtgcgtgatg catgccatgc 9480 catccaatac atctcgacca tattcacata tctgttatcc tttgggtcgc atccggtgta 9540 ttcatgaaac cattcctcaa actgctcttt acttgtcatt ttcacttcct ccactatcca 9600 gcccatcttt ctacggttat tggaaataaa ctcatccgat gttacaaaca gagttctgcc 9660 agatttatgc ttaatagccc atctcattta gtacatcctc agcaagtttg cggaacatga 9720 tttgcactct cgccaccttg cgccactctg cctcggtgag aattacatcc tcatgctgcg 9780 gcactccaga aatctcacaa ggcggaagtg gctcatactc ttgtttcttg cgtttcgctt 9840 tccccatgat gacctcttgc gttgcgaaga agtgaattaa acagatcgct aacactaact 9900 tcctgttcat gccatgagta acgccatagc ttcttgtggt ggtcatagct tcgcgtcaca 9960 tcacagttat gaaacataat gctgatgcgg cttttcacga tgcgataatc aatgccagtg 10020 gtggcgctga tttctttcac ctcagtgcca gcgttatcaa gcaaatggca cttaattgca 10080 tcatcaatac ctgccgcatc ctcagagatg aaatacttgt actgccactt atcaccacga 10140 atcactgact tctcacggcg aataaagcca agtgcaagca tctcatgcaa acgatgcgtt 10200 gtggtgcttg agtgctttcc tccgcaatgc ttttcaatgt atgcgcgcgt tgctcctggg 10260 tgattaataa tcacgcgcat gatttgtgat ttatagtaca tagtcacgct cctctgctgc 10320 ctgactgaaa tcttcggctg tgtataggtg cccgttgcgt gtattccatg acttcactgc 10380 tgattcttga tggagccact catcagtact gcacccacac tgcgagcaag caacgtaata 10440 gccatgaatg tttttgtcat tgtatgcgtc attgctgcca cagaatgggc actccagcag 10500 tccttcatca ttcatcatcg gcatatgtgg tgctgtcatt ttgtcatctc cttaactaat 10560 ttcttcatgt ttaagtcgca caatcttcgc agaatcctgt cgcgtcggta atgtttcttg 10620 ctggttttaa acattgcttt caaaaagcca atgccgccat accaattctt ttgattcctg 10680 cttttcttgt ttctggcgtt ggattccctg atatcagcca taactaattg gtgtatcgtg 10740 ctgcatttgc tcatttcacc cactccccaa gattattaaa tttaggcgta tcgcccgacc 10800 agtcgataac gtccttctgc tggctgcgct tacgttgcag tcggttacgc acttctcgca 10860 actcgcactc tatccactca cgagtgcgct caacttcatt cagtcgctgg attaacgatt 10920 cttcgtacag ttcatctgtt gtcattggat gttcctcaaa atttaccagt tgttgccatt 10980 ctcagtagct caagtacctc ggttgagtaa tcgacctgcc cctgatgata cccttcaagg 11040 atggcgtttt tgatatgcac aagacacagt tcaatgtctt caatatttac tgctcgcgcc 11100 tcaagcatgg agcgcaaata ctcacatctt tctgttatta ctttttccac gctcatttcc 11160 acatcacctt tttcgttgtg gtacaatcta cgtcaataag tattgactaa gtgatgtaga 11220 ttggtcaaca ataattttcg agaaggagta gtaaatatgc caagaccacg acgagagccg 11280 atggacatta tcaccagcat tgtggagaag cggcagccgc tgacactccg cgatgttcgc 11340 tactttgccc gttgctatgt ggcacttgct gatatgccta aagatgagat gtataacctt 11400 atcagggaca acttcaatgt tgacgagaat aacaaagtca caatgaaaag gggtgatgat 11460 gaattggaat gatgtatttg aataccgtga tggtcagttg tattggaaga taaggcctgc 11520 gaatagggtt aaggttggtg acattgctgg gtcaaaaaac aataaaggct atcttttatt 11580 tgatttcaaa ggcaaaaaac accctgcgca cagggtgatc tgggaaatgc attacggtac 11640 tattccggat ggaatggaaa ttgaccgcat aaaccacatc cgtgatgaca acagaattga 11700 aaatcttcgt cttgctagtc atgcggaaaa tacccgcaac atgtcaaagc acagatacaa 11760 cactagtgga gtgaccggtg tgtgctggca taagcaccaa aggaagtggg tagcacagat 11820 aatgtttgac ggaaagtata catgcctagg ttattttgtc gattttgatg aggctgtaag 11880 atgcagaaaa tcagcagaat taaatttagg atttcacagc aatcatgggg atttaaaaag 11940 aaatgaacct gaatgacatt gatgtagttg agactgttaa atacaacaaa tacctgcacg 12000 agattaagcc aggtatattt gttgatgtgt acgatgtgct catggcgtgg aatgttacca 12060 acccggcatt gcagcacctg attaaaaagg cgttgcaggc tggcgatcga gggcacaaat 12120 cacgcgaaca agatttacag gacatcattg acagcgcaac tcgcgcaaaa gaactggaga 12180 ttaaataatg tcattctgcg acatcacaat cgcgcaacga aacgcgaact acaccaacat 12240 tgctgacact tccgcgcaac tggtatcatt gaacagcgac ggcagtgcgg tactgaaaat 12300 cggcacggaa acagcgcaat tcatcgtgca gaatctttct caggcaaacg caaagcaggt 12360 gctgattagc actggtagcg ttctgtttct gggtggcaat tacaatgcac ctaaccttga 12420 gtgttcactg gtgcgcatcg ttgaagctgc ggttgaggaa tctgttgatg agccaacaac 12480 attgccagca gagtgagcca ccaaaaccat ctgcatggtg tgagcaaatg gaacgcaatg 12540 cgaaagatgg tgatgaggcg tatgcttatt ttcagctgaa gcagatgtgg aagcaacgag 12600 aaaactcaga gcaaacaaat taaacacaag ccccttcacg gggctttttt gttgcgtaac 12660 gaattgtact gcgcctcaca tgctaatcca gcttctcttg ctctatcagc ataatctgcc 12720 agttgtcgat ttctttcgac agattctgag agcaattggg caagcaaaac tccggtatct 12780 gcggctggat tgccaatgga ctcagcggtg gaatatccga cgagctgctt gcggatattt 12840 gcgagttgtt gctgcaacct gccagactta gcagcagcat tgacagcatc attgcgcgca 12900 gcatcaatcc tttgctgtgc gtcggcctga atcttttgca gttctgcatt gcgtcgttgc 12960 tcctcttgtt cgtctgcggc cttctgttcg gtgattgctt gagcttttcc ttctgcgtac 13020 cgttggtcgc cgtattctat aagctctccg cgaatccata gcgcgccagc ggcaacaatt 13080 ataataattg ccagcggtcg ccagtattta gcgagaatcg acatcattgc gcagcctctg 13140 aaataactga tagttatcaa gaaatatacg catcagttca tatgaccatt gaatgccgta 13200 ttttttcctg atgccaagat aaagcgttct gtactcccac attctccact ggtggctctt 13260 gatgctatct ggtgtgaagt cggaggcaag tgcaatccat gcattattta tcattgcgca 13320 gcctccggtt ttccttcctc atgccgtgca ttttgccgag gataccaacc agcatgattg 13380 agtagctcac ccctttaacc acgattggcg gtagtgccgc cttcaggtcg tccggcatca 13440 ttacccacac atgcatcatt gcgtcaggcc atagctgcaa cagcgagcag agcgaaatcc 13500 acgcgccgag cagccagttg cttagctttt tcatgccaca actccgccag catccttgta 13560 cacctgaatc agcttatcca gtttctgctc gtgctgacca tagccagcgc ccggcaatga 13620 agcccagcgg gaacggcatt tatggatggc atcagcgacg cgaccagcct caatatcggc 13680 agtggccttg cattcgtgga ttagctgcat tgcaatagcg tcctgtgatg cgggggagaa 13740 gtcaggcaaa cgcagttgct ttttgtatgc atcatagaac ttagccagca cctgatagcg 13800 cccggcggca gtggatttga tacccagctt aggcaggcta atcagctttc gcgggtgatc 13860 ggaatagtcg gcaaacagtg agccaccaac aatcacatca tagccgtgat tattggtttt 13920 ctgccgccca ttatccgttc cctcgctgta cgccagcata tccagaaacg ccttcatgtt 13980 tttactaata gccataccag taaacctctt tttcagcctt gcgttttgct ttgttgtctg 14040 tcttctcgcc ccacacgatg aaatgcgcga cgacgcatga gaaacagcgg agattgtgtt 14100 tcttcagaag cgctgattta cggaacacgt caatgccgat atcggcggca aggcttgtta 14160 gcgcgtcgaa ctgattctgc gttgtctcag tggtgatgta aggagatatg tccacagcat 14220 caatgattcc aagcacctcc gcggcgcgct ccgatagttt cattctgcct cctgttcaaa 14280 taatgattaa ttctatcaca acaggtattg acgtagattg agcggtggtg catagtatct 14340 acatcaaatg atgcgtgagg taataaaaat gaatccacgt gatgttacgt tttacagtga 14400 gtcaaatccg aaggctgcaa aggttgccaa caaaaaagca aaggtgaagc aattgatggc 14460 tgccggtcac accaagaaag cagctcaacg catggtcaaa gaaatgaaat ggatgagtgc 14520 aaaatggtaa tggtcaaact caaagaaaac ggacgctgcg gagtattcaa ccttgaacaa 14580 atcaaaatcc gtccgtgcgg taaagtggtt gcgccatttg ggctggtgca gatgcgcgaa 14640 gttgagatta ttgagtacat taagtgaggt tgcatgaaag agtttaaagg aaccctgggg 14700 tcgtggcatt acgatgatga acttggtggg gtctatagta aaggcggcca attcgtgtgc 14760 gatgttaccg ataaggataa tgccaacctc atcgccgcag cgcctgagct tctggaggct 14820 ttgcagaaaa tgctcagcaa agcgtataag caaaactgga atgatgcata cccagaagag 14880 cttaaatcag cacaggatgc aatcaacaaa gcactgggag aatgaaatga aacttatcga 14940 cctgttagtt caagaattac ctaagcgtgg cgggtggcct cataatgctc tgtcaattac 15000 tcaagatgat gacggtttgc tgtgtgtatg ggacacgaat aatccacact atgatggatt 15060 ttcatggaaa catcacactg ggaatagcct tgtgtattac tggcatggaa ttgaggacgt 15120 acctttatct tgcgaccaca gggagtcgat agtgacctat tggcaatata aagcagcact 15180 cgccgcatcg caaaagccaa catggaacgg agaaggcgtc ccaccagtgg ggtgtgagtg 15240 tgagatatca ttttctggca aatcactagg gcagtgtgaa gttctttttg ttggtgattc 15300 acttattgtc tggaaacaga agtcatcaca gcaagaaggc agcggctacc acaggcatat 15360 gaacattcga ccactccgca cagaagcgga aaggaagcac gaggccgtgc tcgaatctat 15420 ctgcgcggta ttaacaatgg tagcgcaaga ttacaagcga gaggatgagg ccaaactcat 15480 ttatgaagcc atcgcagcag gcaaaattcc cggcgtgaaa ctggatgatt gatatgtggc 15540 ctatatgtaa gcattgcggg cgcatgtgcc ttacgagctg gtgcagaaaa tgcgataagc 15600 catcgaaata aaacaaagcc ctcacttaga gggctttttg tttgcggatt gccacgcttc 15660 tcgctgctta tcaagtcttt cctgtgacga ttcaagaatg acgggtttgc catccattaa 15720 cagtgttgga atttgggcac agtgacaatt atatttatta ccattctcgc tatagaacgt 15780 gtcaatctct tctggcgtgt aaaaccgtcc gtgtctcgct gcgtgtgtct ggcgagttgt 15840 gagcattaat gccgactgcc acagcatcac cgtctcaata cctaattcct cgcgcgcctc 15900 aatgacttct cgcctgttag cctgcctaag cgttccggtg atttcagtct gcgctatctg 15960 tttcgcgtag ctgtgagata catcgacacg cttaacgata tcatcttcaa tatcgcgagg 16020 gttagcgcca cgggcaatgc cttccatgat gactgatgcc agttgctggc gggaatagtc 16080 actcaatccg cgccaatcgg aatagccagc tgcataggca agttgaagcc tgttcaggta 16140 tggctcactg tagagtatcg cagcaatcgg cctctgttct gcataaaccg gagacaggct 16200 tgacagctct gaatttgcct tttgcgttcc ggcctgatac gcatcaccaa tgaacacgtt 16260 ggcccacatc ctgccgtgac cgaaatcatc accttcaaga agaatctcgt caatcagcgc 16320 ctgcaattca tccatgaagg aggctgcgcg cgcactactg aaatcgtaga aatacagacc 16380 gcttgattcg gagttggttt gaccatgcgg aatggtgcgg aacaactcaa gtgcacgact 16440 cctgagctgt ttgtatttgc gcgttatcac cttgtccatc tttgacaggc gagtcgcagc 16500 gcctaacgga tcattcaggc tctgcgatat gcgcggctgt ggaagtctag cgttaaaccg 16560 gagtatcttc attttcatct tccggaggtg tgtcttccat atatccatca ggcatttcta 16620 taggctcaag cccaagaaat cccctgattt catcatctgt aaggatttga ccgacaccag 16680 catttgccgc actttgtgca gcctgagcga gtttaacaat caattcagcc ttgtcgttct 16740 gcgttggttc aagaaggtca ttccacttgc aataatatcc agcgactggc gccttatcca 16800 caatgccaaa cgtgattaaa cgctcaacaa aagagccaac cagataatca agccagccat 16860 cacgtcgttg catagccatc attgccagtg actgctcatc attggctgat gcaagaacgc 16920 cgcttcgact tccaagcaat gagttaagag ggatattcac tgatgcggcg aactgactag 16980 ctgcaacata cataaatggc tcaggatcgc tcattgccgt tgacaggaca cttacgtcac 17040 tgccaaagct aaacattgcc gcgtcaatgc cagagttgag catttctata ttttcattta 17100 gcagatcggc aagctcctca acttcaacac tcatctgctg tgccaatgac tgagctgaga 17160 cgttatcttt attgaaagaa acgttcagtt ggcgcgatga gtttttgagt aatccctctg 17220 cggagctacc ggaaacctta gcgcaatcta tcagggagtt gaatccagcg cgaagtaaag 17280 gaacaccgct gaacatgctg ccgtcaaagc taccctctgc cagaataatt atgcggtcag 17340 ggtgaatctg cacggaacga tcaggcttgc cgtcactatc gaaatcttca acggcacttt 17400 cctgatattc gtacatctca ggcataccgt agtcttcgct ggcttcatca ttattccacg 17460 cactgacgcg gagttgctcc tcccacaccg gaataaagcg aacaatggat ttatctttaa 17520 tgcggcgagt tttggtgacg tctaccggct cattccactt acgcccatca cggatttgca 17580 gtattagcgc agaatatcgg ttaatcagat tccgcttatc tgcatccctg atgaatggaa 17640 gcgccttttt cagaatgtca ttgacgctct tttcccacgg tgaagtggct tcatcatcag 17700 cgtcattctc aagcactgta ggcataccat gccacgactt gttaagaacg atatttactg 17760 cggcatttgc cagcgggtaa cgttcataag caaaccggaa atcctcagcg ttaatttcct 17820 gcttgtaccc gcattccgtc cagagtctgt cgtgcttctg gtccagattc ttcccgccag 17880 cacaaagcct ttgttgctga atcgcccggt tattgttagc cacgcggtcg cgtatatagg 17940 cgtttaaagc gtcgagtttt gacatgattc accaataaaa aatccctcac gatggaggga 18000 ttatagcatg gatggtatat gtctaaacct tatacgggta tcgctttctg aactttccaa 18060 gcccgcaagt aacattgtat ggtatgcagt aaaaatgaac ctgatagcca cggccagcgg 18120 caacaacatt aactacggtt acgatttcgc ctctgtggtt tttatattta ccaccaacca 18180 tctcatctct gatggcgttt agtgtcctga agtgcatcac ttcacctcta tttgaaatat 18240 tgatacagca aacatggcac aacgccagtt accacagcga aaaatgaacc aaccataaag 18300 tgaatcaatc ttggttcatt cactccggca gccatagccc gccagaacat aaagttaagt 18360 ggaatcaaga gcgaccataa tagagccatc actccacctt ttcgaattta tcaaaaataa 18420 cagaaagatt aaaagcgcag ctttcagtga tcgcctggat ttctttcact tatgctctca 18480 tagcgtcctc atatgcaata actgcatcag ggccaattga taatccgcag aaactaccga 18540 cgctcgccac gcttccttgt cgctcaatgt gacagcaata aaaataaacg ctcatcactc 18600 aatctcccat cagttcatcg cgactatact gttttctcat attcctcttg gttactatca 18660 ttcttattgc agcaactatc ggcattgaaa cagggaaaga gatgagtagc agtaggcaca 18720 ataagccata aaccatgtct gccagcattt tcttatcaag aaaatcacca acagtctcct 18780 tcagccaacc gcaatatccc atcctgtatc tttgcttggt attcatcatc actcaatctc 18840 ctcatcatta acccagcttt gcaggacttc gataagctgc gcggcttgtt ttttatcaag 18900 ctgaacccag tcgtcacatt gccttaaatt gattactcgt tctgtattta tatacagact 18960 atggcattca tttgtttttt cgataaccat caaatcaccc tctcaaaaaa tcattcttgc 19020 agcagatacc cttgtatccg cgcttctctt gcaggttaac gaagacatca tccagagcgc 19080 gcagcaggaa gtcctcgtcg atatcatacc gacggcaaat cacatcatca ggcacaccag 19140 cccgcgccag tgaataaacc tgttcttttt cctcctgtgt aaatcctgca tagctgcgca 19200 tagtgatatc tcctttaagc ctgatgtaga ttatactatg cgctcggtgt agattggtca 19260 agtgtggtgg cgcagattta taaacattaa taataaatgt tgacatagat atgatgctgg 19320 tgtagattga actcatgaaa cgaaaggagt gaaatatgaa agatgttaag tttaacgcaa 19380 agaaaaataa atttggtcgc atcctgtttt atgttatgga ggacaacaag catctttatg 19440 agttcaacaa aatagaggat gcagcggaat ggattgctga acttggtcgc cgagcgttga 19500 ttaaatgaaa caaagccctc gattgagggc tttgttttta tcgcctgcgc cggattaaca 19560 tcccgctacc gcgctgaacg atgtggtcac caaggccata gcgcaaactg tcaatcgcgt 19620 gattgtattt atcaactatg tctgggagta tgttccctgt taatttatcc accttgtagc 19680 tgtacattgt catctcttca atgacgttct tgcatcttga gtgtacgtaa atcctgtcac 19740 acccacgcag ccacgtaata ccgtcctcaa tgctccccgg ccattttgcg cacggatgaa 19800 tgtcgaatcc agatcggcgt atatggctta ttgtttcagg ccttgcgcaa tccccatacc 19860 atctgtactt ctctgaattt ggaaatgctg atctcatcgc ttccggcgtg tcagttatct 19920 caaggccaac ctttgcaaag tcacgataga tatacaggtt tctgcgtcca tcgcccaaat 19980 cttctacata tgattctgtt gctgcggttg catcctgaga aaaaccaaag tcaatgccat 20040 aatatggccc tccccattcg ggagatggct cgaagtccag cgtttgccat ttcccgccaa 20100 gcacggcctc ttcggaacgc ttgttgaata acccttcata cacccacaga tagcgatcat 20160 aatccactgc cttcatctgg ttcatgtgct gtttaagttc ttcagtgaac cacgggttgt 20220 ggacgtagtt aacattaaca acaacaatgt catcatcctg atatatgcca tcgaccatct 20280 tgtcgatgta aggctcaaca aagttagtcc acgttgggtc agtctcttta ttcgggttaa 20340 aaacaataat aatttcagag ccagccgcac ggactgtcgg gattaatgta tcccatgaca 20400 cctgactgat attttctgat tcttcacaga atacatctgt aagaccagcc atacctttga 20460 tggcggttat gtttcgccac aggccgcgaa aaacaaactt tgacctcgtt gaatggtgcg 20520 ttatctcacc atcaacgcaa cggtattcct gagtgtggcc cttcctgttt atctcatcga 20580 ccagctctgc atagcttgat tctttgattg agttctgtat ctcacgaaaa caaccaacgc 20640 gactgttgcg gaaccttgcc ttttcgataa ggtaggatat acacgttcgg ctcttggaac 20700 tgcccctacc accataaaac accttaaagc gccgcgggta aaggataagc tccatccgct 20760 caggaattaa tattgttggc tcttcatcag tttcagatac accagtggct gtcatcttaa 20820 ggcgctttac gacattggga gaaccatcct gaagtagctt atctacaagc ccaaaaactg 20880 ctgattcagg ctttgcagtt gagttgccaa ctacctgttc aagtttttcg attgccacac 20940 ttgagagtct ttttctagcc atgattacaa aactccccgt gatgtttctc tctgaactcc 21000 gccacagctc tctcagcatc ttcttgtgat gaaaacctac ctaccgtata ttttttccca 21060 aaaaccctgc aatgcgcctt ccatttattt ttctctgcat cccaactcac accttttact 21120 cctgacgtat ttgtcgatgg tttaccaaca ttccatccgt tttcattatt acttgcttct 21180 ctcaggttgc agattctgtt atctgtcttc acgttattga tatgatctat tttcccattg 21240 ggccacacac cataaatgta aagccacgca agccgatgag ctttgtgtaa agacttatcg 21300 atgcgtatat ctatatagcc tgacttattc ttactgccag ctgaattacc aactcttacg 21360 ctttttgagg cgcgctgaac ccatgtgaaa acaccagtat ctggattgta atgcagtaga 21420 tgcttaagtc tttcctgagt gagagcgagc tcttttaatg atggcattct tgaatcctcg 21480 gttacaggcg gtctattgat tggatgcggc agcccggaga ccaatccggg cagggagcta 21540 ccctttgccg cattaattat tataaatcag ttactgttgt tgctccagca gtttctccag 21600 tcgctcaagg cgagcagcga gttcggtaac ttcggcaata tcaagaccag cctttataac 21660 ctcggcaaaa gtcttgccaa tgtccacagg tataacgcca gcagctatgc cacgaataac 21720 agcatcaatc ttctctaccg gagttccgtc atcagggaaa tcaacttcaa aaacaggggc 21780 gacaggctta ggtaacggac tgaatcgaac gataagttct ttcatcattg cggtgtcacg 21840 ttcaatcatc gccatctcaa cgatggtgtc atagagtttt tcctcgctaa accccttcct 21900 ttcaagagct tcaacgagca acttacgctt gtcttttccg cgtttatttt gtggttgatt 21960 ttctttactg aatagctttt tagccataga taaaacctat caatattccg ctatttttcc 22020 gttattcgat attgtaacag attctacacc atagggttaa tggcaaaaaa agaacccgca 22080 caaggagggt taaaggttgg gtgatgatat gagtgaaagc aatggtggtt attagcttat 22140 tgtacaccat cattaccacg cttgccagca tagcaccacg cattttctgt tcgcgtatgc 22200 acatgaacga tttcaagcgc atccgggaat gtctttgcta ccttcgcgat gaaatcgtcc 22260 agctggtgct gtttggcgat gtgccagacc ttttgcttag ttgtttgcat gctcaaaacc 22320 cctcgtagag cacatacact taatatcgtg aacaccatta tcaggaacaa cctcaatgta 22380 attacctatc tgcaccatca tgtagtggca cgtcttcatg ctgttccagt agcgttccca 22440 catgttttgc attgcgtcac tgatatcgtt aaacataatg caccactccc gcaatagctg 22500 ctaccagtgc cagcacataa acagcaagga agattttagc gccagtggtg tatcggcgtc 22560 gttggtttct ggtcatccat acatctccac taaaacgtgc gcacatagag cgcactgata 22620 attaatatga acgggtagct attcactttt agccaggctt tcgaattgct gtgctgtggt 22680 gtcaaactga accagactga caacatcgtc gaacatgaca aacccgccat cagggtcttc 22740 actcatgtca gcgccacaat cctgaccaca cgagtcgcaa ccaccagtat taagatcgta 22800 tcgcgtgagt tttgcgatat ttgataaatt cagcgccagt acagccaggt cataaacctc 22860 ttcggcggta taacctgcgc catgaccata catttcaatg cgggatatga tttcttctac 22920 tcgttgtttt gtgattgtca tttttgctca ccttcatgtt cttccagaaa aatacgcata 22980 gcataaagca tctcttcggt gtcatacggt gacaacttgt cacgcaggat gtgttcaatg 23040 ctgttaatga acctgcggat tgctttgttt tcgatttcag ccagggaagc atcggtgtct 23100 ggcgtttcag gtgcgtgcat aattgctacc accattgcgt catgcatgca gtcaatgtcg 23160 caacaaccaa cagcttcagc agttttgaac tcacgataca tattgctgaa cgcatctgtt 23220 ttgcaccatg cgtttatgtc cttaaatgct gcattctccg ctgccagcgc agcgcactta 23280 acttccaggg tcgcgtagtc ttcgtagtca acataatcac cacatggcga ttcgtaagac 23340 tcaacgccac caagtgaaac tctcatgtca taacgcttaa cttcactcat accctaaccc 23400 ccataatttc ttcgtaataa ccatctgatt gtcttgctgg catacatttt gttttgcaca 23460 aataagaact catatgtttt tacttttcca tctcaaacac catcggctct gcgattccag 23520 tcggagattg cctgttctgc agactccctg aagtttgtca ttctcgcccc gcatgagcat 23580 cgaatgagaa agtatggttt ttcatggtca gatgagcgcc atggcttaac ctttggttca 23640 ccaccacaaa acgggcattt ctttataatc aactcactca tatcatcacc atatacatag 23700 ctgaatcgtt tacaattcaa taaaacaaat caaagctgat agtttgcctg cccagatatg 23760 attaactcgt ccagcacgca tctatctcca tctctgtgcc atacgcgaca caccttagag 23820 catcttggag agctcactgc tcgctcaacc tgcttgctca taaagttttg cgcgccaacg 23880 tgaccgagtt cctgttccag cttttcgcgt cgatagatag tctttgccat ttgttacgcc 23940 tcgcatgaat taatgattgc cttaatgcgt ctacgatacc actgcattat gtgctcgtta 24000 tgccagttgc tcattttgtt actccttata ccctgatttt gaaacttcca ctgcgataat 24060 gatgaatgcc acgataacca gacttgctgc aagttcgaat gatgcgcctg tcatttacct 24120 aacccatacg ccgagattaa agcctgcatt gctgcgttcc agaatgcttc tgcaggaatg 24180 ctgttgtttg tgcgctcaac tgcgatacgt gccatagcct gtgcatcttc aaattcttca 24240 cggtctttta ttttcatatc ttcaccctcg tttgtttcga tgagtccaat atacatcaac 24300 gatgattcta cgtcaataca atgactaaaa caaaccaaac tgttagtgat aaccaacagt 24360 tattaatttt gtaagtaatt gatttttaac aggtgcattt atccgtttta tcccgctgat 24420 tttttcattt acccaaaaaa actcgtcata aatcatgatg ttgcgtagtt ttatcccatt 24480 tacacttatc ccgaatctaa tagagagaaa tataattttt ggaatggatt tttggtgaca 24540 aaaacatggt gagaaaaatg gtataaatcg gataaatagc agtatatata aatagtaata 24600 gtaataaata catatactta gcactaaaat tacttatccc aaactttccc cgttcttatc 24660 ccgttttatc ccgaattaca tttagcggat aagtgatttg cgcatgttgc ggcttggttg 24720 acatgggtaa tggataagaa taagatacct gatgtataag cgtgaggagg ttttaatgaa 24780 ggtaacaatg gcaactcaat ttgatatgga taatgcaaga aagagaacaa agtggccttt 24840 tagtaggatg aagcaaggag aaattgtttg tatatcagaa tgtgaataca gcaatacaaa 24900 ggttcagaga aaagcccatg cttatgggca tgcaacagga aaatcattca catgcaaatc 24960 aagtgatggg aaagtaatca tcaaaaggat ctcatgatgt cgataaaaac catttatgac 25020 ctgacggcag acataaacaa agaaaagtgg tacgacatta ccaaaccacc tggtcttgct 25080 ggtgaaattg ctgatgacat tgccgctggt gaggttcgtg aacaaccaag acttagagct 25140 gttgccgctc ttcatgaact gattattgcc agcaagggta agattaaaac accaagcggt 25200 atgaagggaa atcttcttac tatctgtatc gcagattcag ctgggggaaa ggataggtca 25260 caaagccatt tcaaaatcat ggcgagagat atcgaaaagg gtatgcatgt atttggtcgc 25320 attgcatcat caaaagatat cggtcggtca ctgataaatc atgatggcgt agcgacattt 25380 attattgatg aatgtcatgg attgtttggt gtaatgactc agaagaatgg cgcagcttac 25440 atggctgaac ttggttctga aattctgtct gtttattccg acagactgaa gaagttctcc 25500 gaccttgatg ctgttaacgc caaagagcag cttgagaagg aactcaagaa gctgaaggct 25560 gaagttaagg ataaagggat tgtagagtca gaataccgca ggcgcgagca gcagcttgag 25620 cgtgaaatat tgtggccaat tcagcagggt atcgaagacc cgatattctc aatgatgtgc 25680 ttttcaacac cagagaagct gtccagcatt atttgttcag aaaatatcgg aaccggcttg 25740 attggtcgag caatcttcat taaggggaag gacggtcgcg caaggaaatt acgcaaatat 25800 ggccataaaa caccacagtc tctaatagat aaaatgaagg cagtggaaaa atcatcacca 25860 caggttgcaa gatacgaaaa tgatgttgtg caggcgcttg ctgaatcact tgatgacaga 25920 tttgaggagc tggtaaatga tgtttctctt ggcgcggtaa ttgcccgttc attcgagcag 25980 gttgaaaaag ttgcaactgc actttctgct gggaataaag gtgtaattac agaagaaatg 26040 ctgatgtggt cattctgttt tgtttgcgaa agcctgacag acgtcatgag catgctaaaa 26100 gtgaacgaaa gccaggaaga actcggaaca atggccagat ggaatgagat taaaaataga 26160 attgagaata tcctttctgg aagaacgaag gatgacagga tgcctcagtc tattctcgtt 26220 cagagggctg ttaaaacaaa atccctcaag gctcttgctg aggctatagc aaggtctaat 26280 ggggaagatt tttcctatgg ggcaaaaact cttgttactc cagtaataca atctctcatg 26340 gcatctcgtg caattgacgc tgtaggttgc ggttactgga ttaacgacgc aagtaaattt 26400 gaaggtacga aaatgagcgt taaattcacg caaattgttg atggtattgg catgaatatg 26460 gctgcaatga ggggttggcg atgaatatag tgattaatga aaatgttgtt aactgttatg 26520 caacagaaac tcgtcctggt aaagttgatt tcacattggg agctgcggat tgtgattggt 26580 ttcatgatct gtttttccca tatggagact ctcaagaagg cattgaagtt attggcggta 26640 ttttttgctt caaagacgtg catggtaatg gttggagagg cgtcttgatt ggcatagatg 26700 gacatcatac tggtaaaaag tatcagattc acacgtctgg aatcggggaa acaaaagaca 26760 aggcagtaaa aaacacaagg aaattgtggc ttcgtatacg gaatgaaatt gagcataaac 26820 gcaatgaggg tgtgctttga tgagcgccaa taaaaaactc aagtttctta ttcacaaggc 26880 gatagctcta aagttgtatg aacatcgact ttttcttctt gagtgttcag tatctccttg 26940 tggatatggt gattatgatt actccatttg cattggtgaa cgccgtggat ggtttgagac 27000 gtttaatact ctaagtgttg gtaatgattg cgagaaaata aataattgct tgtgctggag 27060 ttgcggcgat ggtcttttta gggctgttta catagataca ttttgtaaga tgggagacat 27120 aatcctgtat tcaacagcta caggtggttc aaaagacaga gcttcgcttg atgccattta 27180 tgcatggagg aatgcaaagc gagagataat aaagattatt gacgatgaaa ttgacaagat 27240 gaaactctga taacaaaaac cctccagtcg gagggttttc ttttatctgc tgactgacat 27300 tttctctatc aactcgccag cgtcataaat ctttcttctg attctcttcg ccatcctgat 27360 tgtgtctgca tcatcaggca gcatcaccgg aagtcctgcg ttttccgcag cgcaaagttc 27420 gtcaaattta taattaacta tgcagcgtaa ccgtgctttc gtctcatcgc taacagaacg 27480 caccacttcc cacatgtttt ccggcgacca gcagcaccag acatgcgcac cagtgaagta 27540 atggcatttc cacgcatcgg cataatcaga taccaggtaa atgaactttc cattgtcttc 27600 tccgattgaa cttatcgcgc cgcgagtgag tttgccgttg atggttgagt ccttgttgta 27660 tcctgcgcgg aaaaacgctc tgaatgaatc accatccatg ccaatgaatg ccacgttgca 27720 cggcttcatt gtgtcagcgc gcatcatctc aaccgcaata agctctccag atttacctct 27780 ggcgacatta acgtcgcaac caataccatt tatcaatgtc cactcattca tcgctacacg 27840 cgtagtttta gccatgattg cggcgacttc ctgctcagtg atgaagtcat cgttgtgatt 27900 tatcttcggt agctctttcc tgattgcatc cagcttttcg cgtgggttca tgttcaggaa 27960 tccactaagc gcctccagtg cttcaggaaa actcatgccg gagagtttca ttagccaggt 28020 gattccgctg ccgctgccgc actggttgca tattgcgcca ccatctcctt ttgtttcgaa 28080 gttatcatca aaacgatacc tgtctttgcc aaggcatgat gggcacggct ggtgctttcc 28140 attgaaaacc ttgctgtcca cattgacgat ggacatgatg gcagcctgcc agttgccgag 28200 catttttggc tcgatttctt tccagtcgta tctcataaaa tcttcctgtt gacgatgatg 28260 tagaatcatt gtaatttacc tacatgaaac aatcaatcgt tacttgcaat gaaacaatta 28320 atcgttacaa tagaggataa gaaatggcta tcaccgttaa gaagtgcgag gtttgcggaa 28380 atgagtttat cggaactgca aaagcaaaat gttgctcagg aaagtgtaga ttgcgcaagc 28440 acagacagaa gaaaaaccca attcataact caaaaacaga taatggaata tcttgaatat 28500 aaccccgaga ctggcgtctt tacagctgca aaaacacatg gaacactctg gcgtaaaggc 28560 aaggttgttg ggcataagaa taaggcaggg tacattacca tcacgctact agggaaacta 28620 aggaaagctc ataggctggc atggatttat gtttatggag aagatattga tgggtatgaa 28680 atagaccata taaatggtga caaatcagac aatagaattt gcaaccttag gatttctagt 28740 caccaacaaa acatgttcaa catgaaaaag aaatcaacaa ataaatctgg tgtaaaaggt 28800 gtgcatttcg ataaaagatg caacaaatgg agagcgcaga catcaataaa caagaagagg 28860 gttcatcttg gtttgtttga caccatagaa tcagcagaaa aggcgattcg tgaattcatg 28920 gttgctaacc ataaagagtt tattaattta gggtgagtta tgcataaaat agacaaaatg 28980 atttcagaga ttgatattaa tctgctgaaa tcctatctgg atactggtga tatcgagcca 29040 aggccctatc agtggttgat atataagtta actggtgatg tgattcgtca ttatgttggc 29100 cctggctatg taacagcaag cgtcggtagc ggaaagtcac tgatgattgc catgatagca 29160 aagcgttttc aggaaattgg ctattcaggg atgattttat caagacaggg cgaaatagtg 29220 gagcaagatg cggaagagct atggtcgctt ggtgtaagaa actcgctatt cagcgcttcg 29280 ttggggagga aaagttctac gtatccaata atttgtggtt ctgagggtac tgttgtaaat 29340 gctttgtttg ataaaaagga tgaatcaggg aatgttattg caaaaggtgc gctttctgac 29400 ttttgcccga gatttctgct gatagacgaa aatcatatgg ttaatgacat tgatgttgtt 29460 aatgatggtg atacgcagta tgcagtgata attaatgagc taatgaaaag gtgcaaagat 29520 aagtacggcc atgagttgag aataataggt tatacaggct caccgttccg cggcactaca 29580 tcaataaaag gtgctttctg gaagaaagag attatcaata tagacaccaa gtacatggtt 29640 gaaaacggtt ttcttgtgcc aacaattttt ggtcttcatg atgttgacag tctgcattat 29700 gacctttctg attttcatgg ttcagatgtt gatggtactc aggattttac caccgagcag 29760 ctcaagcaga tgcagaaaga aatccttgag caaggaactc ttacacagaa aatcatgctt 29820 aaagtgatgg agcttactaa aaacagaaac ggagtattga ttacatgtgc tggcaagaag 29880 cactgtcagg aggcggcaaa atacctacct gaaggaagct attcaatagt tacagaagat 29940 atggggccaa aagccagaag gaaggctcta aaagatgcat acaccgggcg caaaaaattc 30000 acattccaga tagcggccct taccactggt gtcaacattc cgctatggga tacgagctgc 30060 atattacgaa aaataatgtc gctaactctc cttgtccagc ttcttggtcg cgggatgcgc 30120 ttgctgaaga aagagcaaat tgacgccggg tatcataaag aagaccatct ggttctggat 30180 ttctcaggca cgatgtttga gcttggtcag ctgtatgaag acccgattct tgaagaggct 30240 gaggcgcaac gttcaaaacg cagtggtgaa caggttccgt gcccgaaatg cggaacgatg 30300 aacagtccat atgcgcgtcg ctgcattggc aaagatgcat tgtcgccaga tggtcgctgc 30360 gaagagtttt tcagttatat ccgttgcggt ttcgataagc acggaatcag aatttttgat 30420 gatggttgcg gcactaaaaa cgaccctaca gctcgctatt gccgacattg cgatcacgtt 30480 ttgcgcgacc ctaacgcggc gttgaatgag cgtgcgtata cggataatga gtgggctgat 30540 gttatggatt tcaaagttca gttaacgaag gatggagagg ggattttata tcgctactgg 30600 attaatcgtt gcgatggcaa agaaggatgg gctaacgaag tattctatcc atacggcggc 30660 gcgactcaca tgaaaaacat gttcaaggca aaggctatat tccctcacct tgatgataaa 30720 tcaatggctg gaaaaatcct gaagtgccag aacgccaagc aattcatgat gtatgcagga 30780 ttgattaaag cgccaaagcg catcacgcat cgcattaatg ataaaggtcg agacatcatc 30840 caccgaaaag actttaaagg agagcaaagt gaagcggctt gacagcggta tatgggtatt 30900 cgatagcggt tatcgcggag aatgtccgaa agaggagata gaccagatgg gttacggaac 30960 atggatgcaa catcgcttcc ctgatgttct gtggtttcat gtgcctaatg aaactggcac 31020 atcaagcagg gtgcagtttg tactgaagcg ccagaagatg ggggttaaga ctggaatagg 31080 cgataatgtg ataatgactc cgggggtgaa acacagttgc ggaatgattg aggcaaaacg 31140 ccgcgacaaa agtaagagca gggttagcaa ggagcaatcg gctgtgttaa ctgagatgtg 31200 cagtcttggt cattatgctg ccatcgctta tggacttgat gaactaaaaa aagccacact 31260 tttctatttt ggcttgcctt ttgatgtgga ttgatgtaga ttcaactaac aataacaagc 31320 gaggtgatga agatggatat tgagattccg gatagttttg atgctgagtg gcaatgcgaa 31380 atgctacgca atcttcttgt taagttaaac gaacttgatg atggcggtca tgttgtcagt 31440 gatggctatt cattgcttga tgatgcaatg aaaattgtcg aagcgttacg tgaatacagt 31500 ggtgattaaa tgagagtcta tttcaataat gaattaacca atgagcaata ccacgccgac 31560 acagagtaca ttaatggctc tggtttgtgg aacatttatg accgctgtcc cgcagcatgg 31620 cgctacaaag acgaagagga tgagcagtca aatgccctca ttttcggcac aggaagccac 31680 acagctctgc ttgaacctga acgtttcgat gctgaatatg ctcgtatgcc aacaaaagaa 31740 gattttggtg atgacctgct tgttactgcc agtgacatga attcatgggc aaaagaacga 31800 ggaatcaaag gactttcagg gaagtcgaaa gctgaggtga tcaaaatcat ccaggcgact 31860 ggcgagccag tgaaaattta cgatgtcatc cgtgaagagg ctgaaaaagc tgctgtagga 31920 aagcaaatgc tggaaggtgg tgattatgac gccattcagc aaatgcgtgc tgtaatccac 31980 gcagacccat actttaagag tgttttcact ggtggttact ctgaagtttc aatacttgga 32040 gaactaatgg gtgaaccatc aaaggttaga tatgattatt tatctactgg agctgatgtt 32100 tgggattaca aaacagccat aagttcaaag cctgaagagt ttttccggca tgctgcgcga 32160 cttggttact ttatgaagat ggcgatgcag cacgacatgt ttgttgaggc atatggtcac 32220 cctccgcgct cagttaatct tctggtacaa gagaaagcag ctccgtatat acatacaggg 32280 attagacttt cagatgagca attacagatt ggtcgcatcc aattgagaaa tgctatggaa 32340 atttacaaag catgcaaaaa agccaattcg tggccgggtt attcaatggg taatccagtt 32400 atagaaatgg aaacgcctga atggttcaag aagcaattta atttataatt agtgaggtga 32460 tgcaatgggc attctcaaca ttaaaccagc agagcgttcc ggttctcgcg tggtcatcgg 32520 tatttcaggc cagtctggta gcgggaaaac atatagcgca cttaagctgg cacgaggcat 32580 ggttgattca ccagaagaaa tcggattcct tgacactgaa aacggtcgcg gtcgcctgta 32640 ttcaaacatc cttgatggta aattcctgca cgctaatatg tatgcaccat tcagtcctgc 32700 tcgttaccgt caggcaattg aagagtttca ggccgctggc gttaaggttc ttgttattga 32760 ttcaggctcg cacgaatggg aaggggaagg aagttgcacg gagattgctg aaaagcctct 32820 gcttaatggc aaaaagatgg ctgactggaa gcgcgccaaa gctgaacaca agaagttcat 32880 gaatgccatg ctgcaaagca atatgcatat cattgtatgt ctacgcgctc gccagaaaac 32940 cgacttcgca aacccgaagg aacctgtatc acttgggttg cagccagtgt gcgagaaaga 33000 cttcatgttc gaaatgactg tgagcatgat gatgcacgat ggcggtaaaa ttcaggaatt 33060 cactaaatta ccagaagaac tacgcccaat attctttgag tctggtcggg aaagcgttcg 33120 acatggatac attggcgaag cgcacggtcg cggactcatc aagtgggtgg actctggcgt 33180 taaagttgac gaagagtttg aatcttggcg ttcacgactt cagctttccg ccgcaaaagg 33240 catggaagga ttgaaggaag aagcaaaatc aatacctgat aacctgaaag ataaaattcg 33300 cgcaatctgg ccttctctcg ctgcttctgc tgcagaatac gatcgcattg agtctttcat 33360 taatgatgag caattaccac aggtggtaat cactcctcag gataatttcg accctgcaaa 33420 actggctaaa ccgaaaccac aacagccaga accgcaggaa gaaacaaaaa ccgaacataa 33480 accaactcca attgaaggat tttaataaat ggcacgcggc gtaaacaaag taattattgt 33540 cggcactctc ggaaacgacc ctgaagttaa atatgcagca tcaggctctg caattgccaa 33600 cctttccgtt gcaacatctg agcagtggaa agacaagcaa acaggagaaa agaaagagca 33660 gactgaatgg catcgcgtgg tcatcttcgg aaaacttgca gaagttgcag gagaatacct 33720 tcgaaaaggc tcgcaggttt atatcgaggg acagcttcgc actcgtaagt ggactgacag 33780 caacggcgta gaccgatata ccactgagat tttcattcca cagatgggcg gagttatgca 33840 gatgcttggc ggtaaacgtg atgattctgg ccagcaacca caccagcaat caggacaaca 33900 accgcaacgg caacagaaac caacaaaaca acaaagccca caaggaggca atgagcctcc 33960 tatggatttt gatgattcaa taccgttctg atgataaaac taaccccgcc gaagcggggt 34020 tttacactat aatcacacag ttgctaatgt aaccctaact aaagaaccat cagctttctt 34080 gacaagtgct tttagtgagc ttccttccca gtatggaacg aagcaagagt tatcttttac 34140 tgcgctatcg ctaacgacgg ttgggctgaa aggtatttct gctgccctgt tgtctgtgta 34200 gttaaccttt attgatacgg catcactaac acttccagac gcagccccca aagacgccca 34260 tgccgaccca cttccagcgc catttgaatg tgccttaata ctaacggcat ccattgtagt 34320 gctcagctta tgcagcctga tatctaatat gccagtatct tggtaactgt taatcctgga 34380 attccccagc attgggtcaa caatgttagc agcattaacc tttctactgt caacattacc 34440 agtaatacct gatattgtag tgtttggcgc gtctactatc agtccgttag atggggttgg 34500 ctttatacca actaaacgca aaccattaac aatacaatct ccttgtatgt atacctgatt 34560 tgcattgaaa tccagcgtat ttgtatctat tactgaaaca ttggtgaatg tctttccata 34620 tgtaaaccat agtgctccag agcctgcgca atcttgcatc aagacgtttg atacatagcc 34680 gcctttacca tccattccta tgccaacacc tagtgagcca atagctacaa ggtcatcaat 34740 tatgtggttg gtcggtaatt gatgtactgg atactcagcc aacgtataat cacctggcct 34800 gtcagtttca ttgccgatat cagcgcctaa atcaaaccca tcccacacag ggtacattga 34860 taatgatttt ctaaactgaa gattgtaaca acgggcagat gtacttccga ccgttccctg 34920 ccatgtctta acacctgact ccccaggacg gaatgacgta aaacctataa caccgccatc 34980 atggtcaacc ccgccatctt ggcgcaggaa ttgaactgag ctaacagaac cgtaagcaat 35040 tctcccacct atacagtagt taccaacccc cttattaccg gatagattca taaaggtaat 35100 tcccgcatcc ccacctgcta ccgccaaatc agaatcaaca gctttacaat aaaagcaagt 35160 atcaaacagg tagcaaccga ccgacccttt agcatttttt acagtaatac cagtacagtt 35220 aaaaatacga agtgtggaat ggatatgttg gtctttcgca taactaggca gcaatgcctc 35280 aattccagga aatttggtgt agtcgcttac ggttggttga taacccctat ccctggtttg 35340 tgccagcgtt gccgcaactg ccgcggcctc cgtaatccaa cttccatctc cattccatgg 35400 aaaaatcatc cacggagttg tggcactttc catatacgga gagtttacta aagaacccgc 35460 gccaagatta gtaaatgtaa gattaccatc tccgataaat ttagctttac agtcgatggt 35520 tagtactttg ccgccaaaat caactgtctc gttgtcggtg aatgtatagt cgcggtcaat 35580 caacactccg tcaactgctg ctgttgctgc ttcctgcaag gtagaataat ctgataattt 35640 tactgaatat ttgaattttt tgttggcttc ctgtctaaat gctgcgtcac caacactaat 35700 ccacgcgcct aaaccaacgc caccagttga tgcaggagtt gaaccagcag ctacagcctt 35760 aggaaatgca ccatcccatc ggtaatattc tccggttgcc tcgtaacgta gcacctgatt 35820 tggtagcgtc aacgtcgcgc catcttcaaa gctatccatt gtgatatatc cataagcacg 35880 aatggcctct tccgcagtgt actggaatcc agcaatagtc cagcgtttta cgccaaatct 35940 gtccacatag taatgtgcat cagatgtcat gacttcatca aatttaccag cgttaaactt 36000 caggtcgcgc gggtcttctg acgggattgg taagctagtc ggtgtggtag ccattataat 36060 aaatgctcct ttgtgaattt gatgtatatt gtatcacgat gacgggatga catattcgta 36120 catgtcatca ctgtattcgc tcatggtcag agttgttgta ccgtcacttc ctggattttt 36180 ctggctgaca acccacagag tggtatccag ttctttttca gtgctcagca catagcgaga 36240 ttcagattgc acgcttgctc catcccatat attcagctgg aaatcagtcg gcaggttgca 36300 ggtgaatgta tgcaatccgg tcactgttgc tggtaatctg tctgatgtgc tgccatcaga 36360 actggtaatc acaacataaa gattatcatc agccgttagt tgctcgcttg ttgtgaatac 36420 gtttccgttg cgcgcttcaa taacgccagt ctgttgcaca tcatcataca tatcgacaac 36480 ctgaatcatg tcaccaacgt tcacatattc cccatccgaa agagccttaa tctccatgct 36540 acgacgggag taaatcaggc ggcgacactc aaggattgcc ctgtcaacag cctgatatcg 36600 attgcgaaca taaagcatgt cgaatttctt ggctttcgtt ggttcgcctt cgactattcc 36660 gctatcggta attcggtagt aaacgttggc ttgcttattc gttgttgggt cgcggtattc 36720 gacgttaacc ccgtcataag tccctggaag gctgatgtcg taacttaact tgtatccgtc 36780 gctctgcgtg tttctggtgt taaatactgt tgctggatat tctcgtttct catcacgcga 36840 aaagctcatc acgccatcat cccagaatgc ggtgactcgt gctgcgtcgc agattgtttg 36900 caggcgttcg ccaatacttt tatcttcatc atcgaatgta tagtcgaaac aaccaagtcg 36960 ctcatcaggc aggctgtcgg caatttcata cagcttcact atgtcgattg tgttttctgg 37020 attgccagcg gtaataagcc agttatgcag cgctgcatct gcaaagctac gggaaggtgc 37080 aagcgtgtag cgcaccgttc cagtatcacg gttgtatccg atggtgtggc gcgtgattag 37140 cgcattatat ttcctgtcac ggctgcctgt tgcgttctct gtggcgcgca caacaacctt 37200 aaccacagtg tcatctggat atgagacgtt tgttctcgtg acgattgagt gaacctcctc 37260 aagctgaaga attgaagtgt cggaactgtt gtttgtccgt cgcatctgga tcgcgtagcg 37320 accagtacca gcagatggtg ttaacttgat cgtgtagtag aacgtatcat ttctgtccac 37380 gtcctgataa tagttcatcg actgatatgt cccgggaatc tgaacgttat catcgtcaat 37440 cttccaccac tcaatgagta cgctgaaatc attgccatca ttggtctggt gttgcaggtg 37500 aacccaaagc tgatcacctt caattggcga gaaatacgga ccagaaacaa tcggctggtt 37560 gtctgtcagg ttgaaatagg tattattaat cgtcacgcca tttagagatg atatcggcgc 37620 gcctgagtag ttgatattat ttataataaa tgtgtaccag tattgggttg gcggtaaccc 37680 tccatcgtct gtttctgttg cagatataag acgaccagac attgttatgt tttcagttac 37740 agatgcacca cctccctgcg cgtaagtgat attcagtttg aacaccacat catgcggcat 37800 ggtaaggtca acgaaataat caaacgccga atccttcggt atcttgactg ctatctggcc 37860 accagcaaat tctgtctccg tgactgtagt ggttgttgca gtctcaataa ccactggcgg 37920 tgggtcggta tccagttcgt ttggcccgta cagttcctgc ccatcaacat catcaaaagc 37980 ataaggctca tacacaacag ggatgacctc ccctggctga taaatagtgt aacttgcacc 38040 agcaagtgag ccgaggtttg actcggagta acgcacagaa gatacatcat acttgccgag 38100 gccaaagttc atgaactcgg tcacgtactt gatattgttt acatattcaa acaatgattc 38160 ctgaagcaaa tcagggaacg cgcgaatctg cccgaagtta tcagggcgcg cctcaccatt 38220 tcgcgcaatg tttgtctgtg ctttcaggct ggtgttaggt gatgttttgg agctggtgtc 38280 cgtttttggc gtggatacct tcggtgtaag gaaggagaaa atcttcgtta ctggcttcag 38340 tatcgagctg ataaggtcgc caattgcgcc ggatggctgg caataaatgt tgacaacgtc 38400 gccatctctc aagcagaaga aaagctcatc atcttcacca agcactctac catttaccgc 38460 aattgaaatg ctggctggca ggtttgattt attcagccac ttccacaggt tagtgcccgc 38520 tggcacaatt cccgtctctt tcggcgttcc cggcatcttc tgaacatgaa ttactggcat 38580 aggtgagaaa ccttaacttt gttgatattt tttcgagtgt tcgcagcctg tcgaatctga 38640 ctgccgtttt ctctcgcgca tgaagtattc tatcacggcc ccatatcatg gcgatgtgta 38700 ccggaacgtt gccgcgatat gccacgacaa catcgccagt tactggtgat tgcgtgtcct 38760 tccagaacgt cacctcgcta tcgaaacagg taacaaaagc gccgccattg tcgtagctat 38820 cgtcatgatg aatattgatg ccacggcaca ggcggtaata aagaaccacc agcccccagc 38880 aatcaacggc gtcaacatgg caacatctgt ccttgtacgg cttgccaaac attaactgcg 38940 caaattcttc atcagacatt acgcagcccg gggaattgag cgatgtcata aagttttgcc 39000 acgtttcctt tgattgggtt tttgattgac agggtcacgg taacgtcaga accatccatt 39060 gccacatcgc tgacatacag gcgatatggc ttcagtggtg tgtttgtgtc agtttcttca 39120 aatcgctgat acagtgcgct gattggctca atacgaccgg aaccagtcca caatttaagg 39180 tattgcttga aatcattcgc cagacgtgca aacttgacgg ttgcgttaat ggctggagtg 39240 ttcgactgct gagactgtgt gatgtccatg cgcactggca gataagtttc accgccaagc 39300 actatctcat ccagcacgtt agccacaagc cgcacataac caaaagacga gtggtaaaac 39360 gttatcgtgt cgaataacgc ccagttaggg cgctttgctt tgtaatcgcg taatgatggc 39420 attattgata ctccagcagg tcacggttaa cgacttcatc cagccatcca aaccatctgt 39480 aatccagttc aaccagaaca tcatcaaact catccatcgt gttattgagt ttcttagcga 39540 taacattgcc agtccatgtg accacgccgc catcaatgct ggtttgcaca ggataatcgg 39600 taaagtgcag cgtctgctcc tgtaatccgc tgccgccgag gtcaatcatc atggtgaacc 39660 agttgttaca cttattcagg tagcgtgagc tacgcaacca ctggataaac gctcgttctt 39720 ccgccagcgt aaaaacccac gtcaggctcc atgttactgc gacgtcagtc gttaattttt 39780 gaaatattgg tgccccaacg gctggggtat ccttcctgaa aggggtttga aacgtaaggt 39840 ttttgctagc tctttgcgcc aaaggcagcc agtcagggta tttgactatc atgtggaatc 39900 ctctttgctt tgttgatgta ttttagcacg gcgcaagttt caccactcca tcatgagctg 39960 gtttaaaatg cattcgttcc atgatgtttt gccatctaaa atagcttgca aaaattctac 40020 atttgaatgt agaatttaat tgtcacatta aacaggagaa ataatcatga aactgcaaac 40080 attagagttc ccgtacggag agatcacttt cgaccgtgaa aattttatta acgttaatga 40140 gcttgttaac cagatgaacc gctggagact ggataatggg atggggacaa gagaaatacg 40200 acaggtaatg gcaactgatg catttaagga tttcaaggct gagtgcgaaa agcaacttgg 40260 tatcgatagc gcaataaaat caacgcgagg caggaatggt tccacttttg cttgcttgca 40320 tctggctgta tatatagcag agcaatacag cacatatttc catttccttg tcatcgaccg 40380 attcattacg cagagacagg ttgagttgcg aaatattggt gcggtaagtt tcgtggaact 40440 taatgctgcc gtcagcagaa tgcttgaacg cactgagggt agaattggtc atagtgggca 40500 tttcattcag gtggcaaagt cagtcaagga gtcgatagat atccgtgaag ttactgggtt 40560 tgacacatgg gactctcagg atgcaaaaac taaccagtta cgcagtgata tccagaagtc 40620 tcttgtcaca cttctggata tggaagcggt caactcatgg gatgaactga aagaaacgat 40680 accgagggtc gtacgtaaat gcgctgataa gatttaaaac aaagccccat aaggggcttc 40740 tttttactct gttgctcgtc tgttggtgtt gtagtttctt gagatggctt gccctattgg 40800 gccattttcc gaaatatcac tcacaatcgt ctcaattgtc acgctgccgt ccccattatc 40860 tctggcgctg ctgctaacct gcgctgagct gttgttgata acgctattat aaaccacaac 40920 accgccacct ccgccggaaa tatccttatt gctgataacc tttcctgagt tgccagggat 40980 catgtattgc ctgcctgtgc tcgcctggaa tatttctggt gcatttccct cgcccacttc 41040 atacatgctt cctgcgctaa cagggccgcc attcttgcgc ttgccagcaa tacccatcgc 41100 cagtgcccca aggacagcgc ctacaccaat tgcagctgcg ccgccgaatg aaccgattga 41160 cgcaacgatt gcagcggggg tccatgccgc cgtcgtggtg gctgcagccg cagtggaggc 41220 agctgtggtg gttgccagtc ctgccgtttg cgccgccgtt gtggtagcgg ttgctgctac 41280 ctgagctgtc tgccccataa ccgcagattt cacccactgc acgcccattt caacaaagct 41340 gtttaccaga gaattcagca ccgtagagcc gaggctgcgc atggcatcct gaacgctcat 41400 tgtgcctgtc agtaatccgg taatgctgtt tgacgctgtg ctcatcgctg aatcaagagc 41460 agtgccgaac agttgcgctc cgaggctttg ttgctgccat tcagcccaca ttgcatccat 41520 tctctgctgg cgatattgcg cttcaattgc tgcgcgagtc tgttcaatct ccgtgatttt 41580 ttgcggatat gctgcggcgt aggcatcaag gtcagccatg cgttgctggt attcactgtc 41640 aatgccagtc gttggtgacg caatggcacg caatccctga tatgatttct ctacgcgctg 41700 cttttccttc tccgcttccg cctgttcctt cagcgcattc ttctggtccc aaatcttcgc 41760 agcgtactcg ccagccagtt ttatttgctc ctgagtggct gccttgccaa gcgattgctg 41820 cgcgttgaga attgcttgct cgcgtgatag ttcgctggta gacgtggcat tgagcatggt 41880 ttgctggcgt aatttctcca gcttctgtga caccgattcc tcaaggtttg cttgttttgt 41940 cgatgcagct atgcgttttt tatcttgctt ttcctgctct ttttttgcgg caagttcagc 42000 tttgtaagcc tctattttgt cgaatgacgc attgattgtc tgcttatccg catcacttgc 42060 cccaagctgc tctgccctgt atatcgcttt ttgtctggcg gtgaaggcaa ttgtttcccc 42120 ttcctccttg attgactgga tataagcctg aagccttttt gtgttttctt cagtggctct 42180 cgcatcctct tctgaagcta ctttgtgccc gttcagcata tcagtagcca tctttgtaga 42240 ttctgctgcc tgatctgccg aaatggaata ttcgccaacc ttgccagtca gttcagatag 42300 agacttgttt gcatatccat atttctgact aaggtcaaca gtcaggtctc gtaattctgc 42360 tattgtttca ggattggcgt tttttctcac cgccgccaga gcttcaacca gcttcaaagc 42420 atcctcggcg cttatgccaa actcatctgc cagacttttt accacctgat taagctggtt 42480 tagtccgaga atattaccct catatgtccc gccaagattc ttgagtgctg tgtttacatc 42540 aattcctctt gctttcagtg tgtcaagctg gctgatggcg gcggatagtg gcgctttcca 42600 tgagccaagt gcgtcgccaa gctcattgac gccctgtact gaagccttga tgatgttgtt 42660 tgcatcaatt agagccattg ttaactgtgc tcttgcggcg ttttctgact gcttagccag 42720 tgttgcaaat ttgtcagaga gaaccacaac accattagca gaaagctgga atatgtcggc 42780 aagacgctgt tgtgcggcgg tcagtgcctt tgtggaaaca gctgcgttat ccatgccagc 42840 aattaatgag ccaacgatta ccgtaccgat ggttagcaat gcaccggcaa ctgcgcctcc 42900 agaaccaaag acgcttaata actgactacc ttgttgactt aaagcaacga gtgccgattg 42960 tccgctctgc acctgaacta caaagtcctg aatctggtag ccgccctgtc tcatggcgtt 43020 atttaaactg gagaaactcc tgccagattt ctcagctgtc gatgcggtgt tttttagccc 43080 tgtgtcaagt ttatttatcc cggcaattga ctcatcaatt gacttctcaa tctcctgaag 43140 aaccttgttt accttttgcc cgccagtagt cagcccggat acatccatcc cgacttcata 43200 aacaattccg ccgacttctt cagccattat gtattcctcg cttttttcgc tttgcgttca 43260 gccagtgcct tcatgcgctc acggtctgct ttagcctgat cgtactcagc cgcacgttct 43320 tctttcgtta accctttcgg ctctggatat ttattcttaa tcatcatctg aaactctgtc 43380 atggacaggt tttcggcctc atctcgcgtc atgtcgaagt gcgtgcgcgc tgagatgatg 43440 tattgcgacg catgaaactc gtttgtggtt ttcttgctct gctcttccag acgctcaggc 43500 actttgagtg gtgacttacc gatgatgcca tgctgcatca ggttgcgcgc aataataata 43560 atgtcgttca ctggcatgat gccaggcacg tatcgcacgc cacgcggagt tggcttccat 43620 ccgccaatca gcacagaaat atcatcttca cagcatgact gcatgacgat ataggccgca 43680 ctcagcacat ggcgaccata cactggcttg ctgatggttt tcatgacttg catctgcgca 43740 ccaaatggca ggcactcgac gtgctgcagc ggcgtaacat aatcaatgcc attgagctta 43800 gcgtacacct ctacaatttc ttttggcgtg ccgatggagt tcatggcgcg gaatgatggc 43860 ttaaagaaaa aactcctgtc ggaaagcgag atgcgcatct ctccgatttc tgttagtggc 43920 gtgcgattgc tcatgttttg catcctgaat ttgactgatg ttgattatat catctcagtg 43980 gtgttgacac ctgctaggtg gtgatgtaga ttcaagtcat cgaaacgagt gatgaataaa 44040 tgaggtgagt tatgaaaatt aaaacgttga ttgcatcagt gctatttgct tcctcctttg 44100 cggtaagcgc aacctctgag gtttgcaaaa acatcggaga aatcgccatg aacactgccg 44160 atgctcgcga taacggtatt agcaagaatc ttgccgaggt ggtagtaaaa ggctcagcaa 44220 aaaacaacga atcagcagaa ataatcggcc ttgctatcgt agaaatggtt tatgcacgca 44280 aggatatgac taaagagcaa ttgcgtgatg tggctgttgc tttgtgcgaa aagaatggca 44340 tgtaatataa acaagttatt aacagttgag gttagttatg gacgttgtta ttttgttgtt 44400 ttttgttggt ttggtgatat ttgcgtacct catgccatct tttgtggctc tgcaacgcaa 44460 gcacgtaaac acgactgcaa tctgcgtact gaatattctt gttggatgga gttttattgg 44520 ctgggttgca gcacttgtct gggcattagt taacagtggc gacaagaaat gaacgaacaa 44580 acaaaagctg acctgatttt ctacactgaa ctgtatgttg atgcagggta cgactatgaa 44640 gaagctgaac gcatggcgaa agatttgctt cgtgtgattg gtgtgatttt tgatgaggat 44700 aaggtgatat gaaaaattat gaagacatga gtgattcaca aatagcgcaa aaggttttct 44760 tttttgtgag tggtaatctt tgccctaacg gagggttagc tcatatcagt tcagatggct 44820 ttttcttttt tgatgaaaag aacattaaga gaaagtttga cccatgcaac aacccatatg 44880 atgcgtggcc tattattgtt gaaaaccata tcgcagtcgt accatatcaa tacaccatcc 44940 cacaggcttg gcccacggca tttggcgcgg cttcaaagtt caccactgaa gacggaaacc 45000 cactccgcgc tgccatgatt gtctttctga aaatgaatga gggtaaatta tgagtcagtg 45060 gattaagtgt agtgagcgga tgccggaaga aggcaaaatg gttctcacgg cgtttcgtgg 45120 cgtggttaga acagcaatat gcaaaacagc cgatgggaat ggaagcaaga tatttgttag 45180 tgaattagac cgctgccacg gaattccaga tacccattgg gccaatccac cgcaaccacc 45240 acaagaataa aacaaagccc ctttcggggc tttttctttg tcaggatacg gtgcacgcct 45300 tgctgataat aatttccggg tcagtagatg aatccgtgac tgtgacggta tatacaccag 45360 cggtagggct tgccagtgtc gcgccagact taccaccaac aaccgcgcca tctttgcgcc 45420 atacataagt gtaaggagca actccgcctt caacagcaac agttaacggg ctgccagtgc 45480 tgccagttga ttgcaggtcg gtagtgaatg ccagaggctc aaggctttct acggtaacgc 45540 tgtcagaatc gtaaaccttg aactcaaggc taccagtaac gatgtcgttc gtgccacctt 45600 cataactgat gctggtgatg ttgcaatacg cggtaacgat agtagcacca gtcacctcgc 45660 gcacccacaa ggaaggctgg cgacgcgctt tcagttcagt ggcgtaaatc tcaaccaggc 45720 gatggaagcc aaattcatcg ctcgggtcat tcttgcggat ttcaacctct gcgctgatgg 45780 tcatatcaga gctggtaacg agagtggaaa caaatccgcc agcggtatcc gcttccgacg 45840 tagtggtctg cggcgagtag tcaacacctt tgctggtggt tgaacctaaa tacttccagt 45900 cttctgcatc aggaactgcg tcaccgcacc cctcagcaag gaacagtcgg gtcatgcgac 45960 cgaccagaac gcctttatca tttgcacaaa tagccatttc gatctccgaa ttgtgttagc 46020 tgctaacgtg gtgattatat cacaggtgtt gacagtgatt attttgtggt gtagattgta 46080 tttcagatgg ttttcgtgag cgactttgcg gactttttag aaactgacca caaagataaa 46140 tgcaaacgat gatgttgttc tgatggcggc gtaatagcct gtaagtcagc aaggtattcc 46200 gattccttgt aagcaaattc ggcgcactgc gtccctgagg tgtgattaat aagtcaggga 46260 acacaacagg aaagagcatc tcgccaagaa gttgatgcga aagcaatcta agaggtgctc 46320 tttccgttgt gaccagcaag accatacaac acgcgcgata atctcaactg tagcatgtgt 46380 tgcgtggctg ggaatgggtt gacatttaag agtgagatgg tgcgccactc cacaacactt 46440 aatatccagc attatcgcaa tcatatgtag gggtatgtat gggttacggg gctggatatt 46500 aagaaagcac gctggcaatg cttaaaccag cacttatgga cgcgtagctt aattggttaa 46560 agcaaccgac tcataatcgg atgattgaag gttcaaatcc gtccgtgtcc accaaattaa 46620 acaccattag ctcaatggaa agagcagtag ccttctaagc tattggttgc aggttcgaat 46680 cctgcatggt gtgccatcta aactaaaaaa ccacaaatca atccctaagc aattcgcagt 46740 aaaaatttca catagaaatc aagcaatata aaggtaatct catgaattta aattcattat 46800 tcacgtatat aaatggtgaa ctgtactggt ctgcaccagc cgggaataac agaattaagg 46860 ccatgacaaa agctggaaca gttgatgata atggatacat tagggttaag attggtaagt 46920 ctaagcattt agcgcaccgc atcatatggg aaatgcataa cggagcaata cctgacggaa 46980 tggaaattga ccgcataaac cacgacaaga ttgataacag gattgagaat ttaagaatcg 47040 ttagcaggtt aataaatatg caaaataaga gtaaatacaa aaacaattca tcaggagtgt 47100 gtggcgtaag ttggcacaag gttaagtgtt tatgggtgtc gtatatccaa aaaaacaaga 47160 gcagggtcat gcttggttat tttgatgatt tcttcgaggc tgtatgtgcc agaaagtctg 47220 ctgagataag cctcgaattt catagcaatc acggcaaata attacccgta aactaccctt 47280 aataacaatt cgtgaacagg cctcttctct tctgttaaca tcatatcgcc aagcggagat 47340 tgcatctgta tgtagttcag gcagctatca atcgggtttt cttttatgta ttcaattat 47399 <110> KYUNGPOOK NATIONAL UNIVERSITY <120> Novel bacteriophage having pathogen Salmonella Entritidis          specific antibacterial activity and use thereof <130> PN1712-479 <160> 1 <170> KoPatentIn 3.0 <210> 1 <211> 47399 <212> DNA <213> Unknown <220> <223> bacteriophage KFS-SE2 <400> 1 aaaaaaacaa gagcagggtc atgcttggtt attttgatga tttcttcgag gctgtatgtg 60 ccagaaagtc tgctgagata agcctcgaat ttcatagcaa tcacggcaaa taattacccg 120 taaactaccc ttaataacaa ttcgtgaaca ggcctcttct cttctgttaa catcatatcg 180 ccaagcggag attgcatctg tatgtagttc aggcagctat caatcgggtt ttcttttatg 240 tattcaatta tttcgttagc tttattatca acaacttcgg catcatattg cccttgctga 300 ccaacaacaa acagcttgaa ataaaagtca tttgataacc cttggcggat acctgttccg 360 ccacttgttt tcaggacaag aaagcgatcc tcgcctactc cagtatcatt ccataattga 420 agttgtgcag tccacccatc catcagtcct gcatcgttta aataattata aactcgctca 480 agcatattca tagtttcatc tccttcttaa tcacgccatc aacaaggtct ttggtgcgct 540 gcgccgcttt ggtcaggaat tgtgtctcac cgcccggcga ccagtatgtg ccattgccgt 600 tgctgcgtgg ccttcctttt agtttgccac tggcgttatg aacatacaga gcataattcg 660 cagaatagcc aaccttgcca gtgattcgcg ttccgttaac ttccacggta tcaaactgac 720 tgttaatcag cgttgatgta tcaattggcg ttagcgtggc tgattcggtg cggatgatgt 780 atgtcgctga cttgattgca cgcacagctt tcgtggcgat tatctcatcc acaatttgcg 840 aagttctctc tacagcctgc cggacacctc ttaatttcgc tggcattatg tcaccagtgc 900 aaagtctgga ggctctgccc tattgaaagt cgaaccgtaa ttaatcacac tcagaatctg 960 atttgcgcca gccgccagtg ggtcagcttc tgtcgccgtg ccaatcatga tgtagtcacc 1020 taccttagct gcagtgtatt ctgtccagaa ggtattcttc tgcacaatct cattaccttt 1080 cgcatcggtc gatacatcat cattaaagcc gtaatcacac atgatgctca ctggtgcatc 1140 aaaagtcggc ttgccgtact tgtcagtgcc gcttttgtgc cagatggtgc atggctgcgt 1200 gtaactccag ttagccagtg aagtcatttg catttactcc cacgcacaac cgcaaaccac 1260 ggttttccac ttccgtcagg gtcttcaacc aaatcaccag tgcatccagc tgtatccagt 1320 agcttcatct gattgtacag cgccacccac ggcttgcttc cgtaagcgaa tgattgtgat 1380 gcgccagacg gtgcgctctg gctggtgacg tagcgaccag ctgtatttgc gccaatcagg 1440 atggaggccc acagcatgat cgcattttgt cggcattcat cacttggata gttcagttca 1500 aggcattcac tgattgatgc tacaagacac agaataccgg acgcatccgt tgtggtgatg 1560 gtcatcccgc gcgatgccat ctggctgacc agttcttcag gtgttggtgc tgtcatttct 1620 ctttgactcc ctaactttcc accacatttc aaacaggttc tttattacca gagacagagc 1680 gccaagaatt gacgctactg ccgcccactc tgtcaggctg tgtggaatca tagcctcaaa 1740 ataagattgc gtgacaggtg tttgttctgc aactttcaga ccgataccgg tgccaataga 1800 agcgtatccg gccttgtcaa tcacctgtcc tgtcgttccg cttataatct gctctgcgac 1860 ttgccttagt gtcccgttca ttgcgtgtct cgctgatgat atgtttccag cacttataga 1920 tttgaatcag cgaaaaaaca atggcgacca cgccaagaat aatgtccaat ttcgccgccc 1980 catttaaaag tgatggaaag gatgaacaga tggatgccga taataataaa tgcgtactgc 2040 gcatgaagcg gcgtttctac aggcgtgata aattcccatg cgaatgactc tatcgctacc 2100 agccattcgt aaaggctcat cgtcagcacg cagagcgcca tctttgtact tttgcgcagc 2160 gcaatagccg gaaacaacca gaccatagac tgcgcaaggt aatacagata ttcggcggga 2220 aatgaatcaa caagcaccca tccaagatac acagacatca ccattgccgg aatgaacacc 2280 agaagcgcaa ccatgcctgt gcaggcaaac cccaacacat acatgatcat gatggcaatg 2340 tctgcgccga acattatttc ttgccgcgag atggtgagcg ggtggagccg tttggcttca 2400 ctgcgccagt tttggtattg ccagtagcgc gcgaacgaga aggtgaattg gtggaaccca 2460 tgtttaaatc ccctgttgtt tgattagcat gattttagca tattcctgtt gacgtagatt 2520 gatggtgcgt ttatagttag tgacgtagaa acaacaataa atgttagagg tgatgagatg 2580 tttgatattg ataacccaag tgatgacaaa gctaagctga ttgatgcagt cgcttgcagt 2640 tttgcttctt gccagacaga aggtgaatat caggttgtga aaatgtgcat tgttgagttc 2700 ttctcggcaa tcaacattcc tgacgatgag gctgttgata ttctgctgag ttccgctggc 2760 aattgcgctg atgcggacga atgcattgat gaactggttg aagagtttgg cggtattttt 2820 cagggtgacg aggagtgatt atgagcagta acgcaaaaca ttatgattat tacatggttg 2880 aaggtgctga tgttaagaat gttattgacg catatgatga catccaaaag cgccgcaatg 2940 aaattctcgg cgatgccatg aaaaaggttg gtgctgtcgc tttcactaca acacgtagct 3000 ggggcgcggt cggaggtggc ttacttgaga gctttgtgtg gagtgagcag tttgaatttc 3060 cgtgccaagt gacaataaag cgtgaagact tttgggaagg tcagcgtgta attgtggctc 3120 gcggaaaagg aaatacaaag gatgggcggg aatacaacaa aaagctggac gcagtgattc 3180 gcgaggcaaa cgagaaatta aagttattgc cagaatggaa ggactacatt gttaaccatt 3240 atggcattgc acgcacaggc attggcgagc aatcaggtcg cggatttggt tttgcaatgc 3300 tgtctactta tggcggtaaa cacccgcaaa aggatgattg cctgattttt gctgtgccaa 3360 atacaaaaga tgaaggtcac ggacaggtaa cgatacctga taactttaag cagataacat 3420 acggtcagtt ttacgatatt gctaattcag gtgatgagga ataaacaatg aaaacactaa 3480 gcaaaatcta ttcagacaaa gaaacacgca atggtatcgc ggttaacaaa acctatctcg 3540 tgccagttga gcaaatctat ctggagccgg ggtacaacat ccgtgaagca gatgagcagc 3600 acgtcgaata tttcgcgcag tgctgggaat ctggtcaacc attaccagca ttaacagtta 3660 ttcctgatga gaaaggcatt cgcattcttg atggtcagca ccgctatctc ggagcattgc 3720 gtgccattga gcgtggcgcg ccaatcgttc gcatcgagtg taaggatttc acgggcgatg 3780 aggcggataa aatcgcgttc atggtgtcat ccagtcaggg taagcaactt gacccgtttg 3840 aacgcgcaaa ggcttacacg cgactgaaag gctttggctg gacgaatgaa gaaatcgcca 3900 agaaggtagg tcgttcagta tctgacgtgc aaatgcattt gtcgcttggt gatgttccgg 3960 cggaagtaaa ggcgcgcatc agtgcaggac aaatcagcta tgcaaatgcc gtagcggtaa 4020 cgcgagaaca tggcgatgat gcggttaaag ttatcgacga agcggtcgaa gaagccaaag 4080 cacaaggcaa ggataaggtc acggcgaagg tgctgaagtc gaaaaagatt aagccagtag 4140 accgcctgat tgagttactg aagccagcgg accacgtaat tctccccgct ggtcatgtag 4200 tggcagagga tgaggagttc atccagattc ctgttgctga tattcatgag gtcatggcaa 4260 ttctggagaa gatgtgatga gtgaacagcc gcttgctttc agacaaatag aaagaaaagc 4320 tattaagagc cataaatgct gcgagtgtgg aagagaaata cacaaaggag ataaatataa 4380 gtattcatca ggaatctcat cggaaaaaga tgctttttcc tataaacaat gcttgatatg 4440 cagcaaggca ttcaatgcag catctgaaat ctcagattac gatgacatgc catgctttac 4500 gggtcttagg gagtggatgg gaaattactt ctctcgaaat taccctgcgc agaaaagcgt 4560 ggatagtata tgcatggact taggtttaac agaatcggaa gttcgataca tcattccagc 4620 taagtggttg gtcctatgaa cgctgaacaa ttcatcgaaa aacaacttcg caccaagcta 4680 cctgacattg accagatggc aattgatgcg gcaattcagt attacaagcg caatcagagc 4740 gcaaagaagg gtggcatttt tgaagaatgc ctgaaggttg caaaacagca tatgattaag 4800 gtgaagtgat gaaactaaaa atcagcaaat tattacttga gtcagcatta atatttcagg 4860 cgcgcaatga tgtgcgctac tacctgaatg gcatttgctt tatgcaagat ggtcgtgttt 4920 catcaactga cggtcatcgc gcattcattg gtggcagtca tgacaatacg ctgacagaaa 4980 atgtgattat caagattggc aaatctccaa caaaacgcta tgactacgcc atcattgata 5040 ccaagtcgaa aattgcaacg tatcatgatg aagctggcga gatggttggt gctggtatct 5100 gcgaagagat tgatggtcga ttccctgata ttgatcgcgt cattccgaag cagaccttac 5160 cagcagagga aattggattc aacgctggat atcttgttga tattgagaaa gtggcgaagc 5220 tgtttaatcc taaattctgc ggtgtcaaat ttgagcttaa tggaaataca aatgccgcag 5280 tttgctgtct tagtgcgcca tctggagata ctgcaaagat tgttgttatg cctatgcgcc 5340 tgtagcaata aaaagccccg tcatggggct tttcttttat tttgcatcca tggaagccac 5400 aataaaaaac ccgcattatg cgggttcagt ttactctgct ttctttttct ttatcgtctt 5460 ttcttgcggg gttgcgactt cgaaagactt ttccagctct ggcatgattc gcagttttgg 5520 tagcagatgc tcatctggtt cggtaatcac ctcgccaagc tgcaactcac gaatcttgcc 5580 tttctcttta acaaagattc cgcgtgcgat cacttcgtat ttagccatta ttcacctcaa 5640 attcacaaag gggccgaagc ccctatcttt attacttcgc aggttgcgtg ccgtatccgt 5700 tgaacacttt ggacttaccg gcgaaatcct tgcgcacctg taatcccata gctgaccaca 5760 ctaggaagtt gaagttatcg tgagggttta cgcgggccgc cgcataggtg gagacaggct 5820 gagcaacacg cggacggatg tacatatcgt tgcgaacgta gccaacgaaa tggttaccag 5880 tcagcaggaa gttggtgcca atctttccga tgcgaccgtt gccgaactgc gtgatgtact 5940 gctcaactgt gccgcctttg aagcccgccg cattagaata cggacgcatg aagctgcgac 6000 gcactgccgg ggaaacccac agagtcacct gctcaaatac gttctgcgca tccagaatag 6060 cctgaaaatc ctgattgaag aatttcacga tttcgtctgg cgttgcggtt tgcaggtcga 6120 tattcaggcc gcccccggaa acgttcaggt taacctgtac agtgttcggg tggttagtga 6180 taccgtaacc agtgtaaacg ccgttcacgt tcagagtctg gtcgccagtc agcaggtact 6240 gcgccatatc ggaacgcagg ttgaaggtga cgttagcctg atcgtccagc agtgggtcga 6300 aaccctcaga ctgcatgccc agcagttcgc gccattctcg gctgtagcca gtcttgaaga 6360 ttggaatcac atcgccagtg taatcgtagc gggttttatc caaatcttcc ggctcctgac 6420 cagacagagt gcgcacaacc ttaccagcat cggaagcaat gcgactgatt gccacggttt 6480 taccgatatt gatgtttgcc gcgataccca tcaggtcagc catcatgtcc tgaccagctt 6540 cgttacggaa aacgcgggta gtgacgttgt ccacgtcgcg ccagtaatct ttcgttacca 6600 gtgcggtggc gttcacaccg taagttttcg ccagctcagc ttctgcgttg cagaacacct 6660 tacggtcgat ggtcagatgt ttccactggt cagccactac tgcggagttg gctaccaggt 6720 ctttggtaaa aataatcttt tccattatta acctccagca ggcatgtaag cattgccagc 6780 gcgacgaact gcaaccagct cagcgccatc agaggcaaca gtataagttt cataggagta 6840 aaacaggata ttatccccat caccagcaac tttcagcgcg ccagcgccgt tgcttgccag 6900 cggagtgcct ttcttcagcg cagaagatgc agcaaccagt gcgtgatagg tgacgccaaa 6960 ttcacactgt acagccatgc cagtagcatt agccggaaca gcctcagaca catcgccacc 7020 accgaggtag ttatgctgaa gcacataagg gaaaccctga ccgccagcgg tagcgtgcgc 7080 gatgattttg tcgtcagcag tatcgaagtc aaccagtgcg cccggcttca acgcgacctt 7140 catgatgcct tcgcgaatct gcgggtcgtt cttgcgagct gggccaccaa tgatggtgcc 7200 ataacggata gtagccatta ttcaggtgcc tccatatcaa aatcgtcatc agcgtggttt 7260 ggctggaagc cacccttcag cgcggcaggc ttgctggtca gcgcataggt ttcacgcagt 7320 gcttcgcctt tcagcgcatt cacagcggat tccggcagtt ttagttcagc gatgatagca 7380 gcacgcatcg cggtttcttc ctgctcggtg ttcgcctgca attgctcttt cagtttaacg 7440 ttttcagctt cgatgtcggt cagcttctgg ttgacagctg tcaacgattc ctgaaccggc 7500 ttgagggctt cagcgagtac cgcctgtaat tcctcgttcg tcattgagat ttccccttca 7560 gttgatttta ccggctcaag ttcagtctta taaacagcct tgacccgctc accgaccaat 7620 tttaccacat catcttcaac gatgtagaac tgctgaaaaa tctggccttt gatttcgaat 7680 ccgacacggt cgtcgtacac agccacgata taaggccaga catcctcacc gacttcagcc 7740 ttcagaatct ggcgaatctg ttcgctgatg ttctcaaacg acaggtctga tttgttggtg 7800 atgtagttga tagccttatg tagccacgat ttataattaa tcttgttggc gctttcgtct 7860 ggcacggttg aatcctcaag gtttacggtg atgcgttcga tttgctcgcc attggtggca 7920 aagatgccaa caccatcttc tggcgttccg gctccctgca ctcccggtgg caggatggcg 7980 aggtggtccc attccatgtt gcgcgcaatc catgagtatt ttttgccttt gctcgtgcct 8040 tccgcagctt cgcggttgag caataagcca gttgatacat ggattggttc agcaccttca 8100 gctgagttca tcagcgactc aatgcgaccg agcaactcct gacctttctc tgagcgttca 8160 gcaataactt tgtttacttt aaggtcaaca agcaccttgc caccatcatg agaagcattc 8220 tctatccatg cgccaacatg atactggttt accgcccgaa tattgtgcgc agaaacgaaa 8280 gagccatcaa ccattgggtg gttgtatggt gctgggtttc catttagccc atgataacta 8340 ttgcgtatct cttccgccgg gtacaggccg ccgttcatca ctatgtcgtc gcatagaggg 8400 gtgacatttt ttataacgta gtgcaagtcg ccatcaatca cctgctcact gatattgctc 8460 gcggaattga tagtggtgag cacgttaact tgcaatctat tcatcgcgta gctccacggt 8520 tagttcgtgg tcgaattata acacagggag atatagcacc atgaggcggc agccagtgca 8580 aataatggcg aattggtgag tgcgtagaac gtgagaaaga aagtgatagg gattatgttc 8640 atgggctacc tcctgattaa atgatagtag cccatgatga acaaaaggta tacggagtta 8700 gtctgaaatc acatcatcca taaatgcgag cgcggcacat gaaaggcaga gcagggcgcc 8760 atagcaaatc atctggtaca gattgtccgc ctcaaacacc cttgcgaatg cgtaggctga 8820 taatatccac agtaatggaa tcatttacat accctcatta ttttgcgact atgaaatacg 8880 tgagatgaat cctctctaac tggcattgtc cccactggcg atttctcgca acgaatacac 8940 tttctagtcc aatatttttg gccagggtta aatctatacc aatcctttga ctcaccacac 9000 ctgtagcact gatacatgcg catcatacca acccagcctc ctgttttgcc cggtgaacgt 9060 atgacataaa cttgccaatc ggcatttcct tgcggatttg cgccagaatc gcgccatgca 9120 acatcctctc ctcgccaaaa tacagcttat cgagtcgcgt tttgatgagt gctcgcgtgc 9180 gcttcatatg gtcgcgtgcc ttaagtgctt tctcatgcca gacgcgatca ttcttcttat 9240 cggcatattg cagttgacgc tcaacggttt cgatttcaaa cgccagttgc atgtcataat 9300 cttcaagctg aatgatgtct gctttcataa tgtcgtttag ttggataatc attttttcac 9360 ctttaatcct gcttgtttga ttgcttcaat aacttcatct gcatagtaaa taacgtgaca 9420 tccaagactc tctacctctg gcaattcaat ctcaatagcc gtgcgtgatg catgccatgc 9480 catccaatac atctcgacca tattcacata tctgttatcc tttgggtcgc atccggtgta 9540 ttcatgaaac cattcctcaa actgctcttt acttgtcatt ttcacttcct ccactatcca 9600 gcccatcttt ctacggttat tggaaataaa ctcatccgat gttacaaaca gagttctgcc 9660 agatttatgc ttaatagccc atctcattta gtacatcctc agcaagtttg cggaacatga 9720 tttgcactct cgccaccttg cgccactctg cctcggtgag aattacatcc tcatgctgcg 9780 gcactccaga aatctcacaa ggcggaagtg gctcatactc ttgtttcttg cgtttcgctt 9840 tccccatgat gacctcttgc gttgcgaaga agtgaattaa acagatcgct aacactaact 9900 tcctgttcat gccatgagta acgccatagc ttcttgtggt ggtcatagct tcgcgtcaca 9960 tcacagttat gaaacataat gctgatgcgg cttttcacga tgcgataatc aatgccagtg 10020 gtggcgctga tttctttcac ctcagtgcca gcgttatcaa gcaaatggca cttaattgca 10080 tcatcaatac ctgccgcatc ctcagagatg aaatacttgt actgccactt atcaccacga 10140 atcactgact tctcacggcg aataaagcca agtgcaagca tctcatgcaa acgatgcgtt 10200 gtggtgcttg agtgctttcc tccgcaatgc ttttcaatgt atgcgcgcgt tgctcctggg 10260 tgattaataa tcacgcgcat gatttgtgat ttatagtaca tagtcacgct cctctgctgc 10320 ctgactgaaa tcttcggctg tgtataggtg cccgttgcgt gtattccatg acttcactgc 10380 tgattcttga tggagccact catcagtact gcacccacac tgcgagcaag caacgtaata 10440 gccatgaatg tttttgtcat tgtatgcgtc attgctgcca cagaatgggc actccagcag 10500 tccttcatca ttcatcatcg gcatatgtgg tgctgtcatt ttgtcatctc cttaactaat 10560 ttcttcatgt ttaagtcgca caatcttcgc agaatcctgt cgcgtcggta atgtttcttg 10620 ctggttttaa acattgcttt caaaaagcca atgccgccat accaattctt ttgattcctg 10680 cttttcttgt ttctggcgtt ggattccctg atatcagcca taactaattg gtgtatcgtg 10740 ctgcatttgc tcatttcacc cactccccaa gattattaaa tttaggcgta tcgcccgacc 10800 agtcgataac gtccttctgc tggctgcgct tacgttgcag tcggttacgc acttctcgca 10860 actcgcactc tatccactca cgagtgcgct caacttcatt cagtcgctgg attaacgatt 10920 cttcgtacag ttcatctgtt gtcattggat gttcctcaaa atttaccagt tgttgccatt 10980 ctcagtagct caagtacctc ggttgagtaa tcgacctgcc cctgatgata cccttcaagg 11040 atggcgtttt tgatatgcac aagacacagt tcaatgtctt caatatttac tgctcgcgcc 11100 tcaagcatgg agcgcaaata ctcacatctt tctgttatta ctttttccac gctcatttcc 11160 acatcacctt tttcgttgtg gtacaatcta cgtcaataag tattgactaa gtgatgtaga 11220 ttggtcaaca ataattttcg agaaggagta gtaaatatgc caagaccacg acgagagccg 11280 atggacatta tcaccagcat tgtggagaag cggcagccgc tgacactccg cgatgttcgc 11340 tactttgccc gttgctatgt ggcacttgct gatatgccta aagatgagat gtataacctt 11400 atcagggaca acttcaatgt tgacgagaat aacaaagtca caatgaaaag gggtgatgat 11460 gaattggaat gatgtatttg aataccgtga tggtcagttg tattggaaga taaggcctgc 11520 gaatagggtt aaggttggtg acattgctgg gtcaaaaaac aataaaggct atcttttatt 11580 tgatttcaaa ggcaaaaaac accctgcgca cagggtgatc tgggaaatgc attacggtac 11640 tattccggat ggaatggaaa ttgaccgcat aaaccacatc cgtgatgaca acagaattga 11700 aaatcttcgt cttgctagtc atgcggaaaa tacccgcaac atgtcaaagc acagatacaa 11760 cactagtgga gtgaccggtg tgtgctggca taagcaccaa aggaagtggg tagcacagat 11820 aatgtttgac ggaaagtata catgcctagg ttattttgtc gattttgatg aggctgtaag 11880 atgcagaaaa tcagcagaat taaatttagg atttcacagc aatcatgggg atttaaaaag 11940 aaatgaacct gaatgacatt gatgtagttg agactgttaa atacaacaaa tacctgcacg 12000 agattaagcc aggtatattt gttgatgtgt acgatgtgct catggcgtgg aatgttacca 12060 acccggcatt gcagcacctg attaaaaagg cgttgcaggc tggcgatcga gggcacaaat 12120 cacgcgaaca agatttacag gacatcattg acagcgcaac tcgcgcaaaa gaactggaga 12180 ttaaataatg tcattctgcg acatcacaat cgcgcaacga aacgcgaact acaccaacat 12240 tgctgacact tccgcgcaac tggtatcatt gaacagcgac ggcagtgcgg tactgaaaat 12300 cggcacggaa acagcgcaat tcatcgtgca gaatctttct caggcaaacg caaagcaggt 12360 gctgattagc actggtagcg ttctgtttct gggtggcaat tacaatgcac ctaaccttga 12420 gtgttcactg gtgcgcatcg ttgaagctgc ggttgaggaa tctgttgatg agccaacaac 12480 attgccagca gagtgagcca ccaaaaccat ctgcatggtg tgagcaaatg gaacgcaatg 12540 cgaaagatgg tgatgaggcg tatgcttatt ttcagctgaa gcagatgtgg aagcaacgag 12600 aaaactcaga gcaaacaaat taaacacaag ccccttcacg gggctttttt gttgcgtaac 12660 gaattgtact gcgcctcaca tgctaatcca gcttctcttg ctctatcagc ataatctgcc 12720 agttgtcgat ttctttcgac agattctgag agcaattggg caagcaaaac tccggtatct 12780 gcggctggat tgccaatgga ctcagcggtg gaatatccga cgagctgctt gcggatattt 12840 gcgagttgtt gctgcaacct gccagactta gcagcagcat tgacagcatc attgcgcgca 12900 gcatcaatcc tttgctgtgc gtcggcctga atcttttgca gttctgcatt gcgtcgttgc 12960 tcctcttgtt cgtctgcggc cttctgttcg gtgattgctt gagcttttcc ttctgcgtac 13020 cgttggtcgc cgtattctat aagctctccg cgaatccata gcgcgccagc ggcaacaatt 13080 ataataattg ccagcggtcg ccagtattta gcgagaatcg acatcattgc gcagcctctg 13140 aaataactga tagttatcaa gaaatatacg catcagttca tatgaccatt gaatgccgta 13200 ttttttcctg atgccaagat aaagcgttct gtactcccac attctccact ggtggctctt 13260 gatgctatct ggtgtgaagt cggaggcaag tgcaatccat gcattattta tcattgcgca 13320 gcctccggtt ttccttcctc atgccgtgca ttttgccgag gataccaacc agcatgattg 13380 agtagctcac ccctttaacc acgattggcg gtagtgccgc cttcaggtcg tccggcatca 13440 ttacccacac atgcatcatt gcgtcaggcc atagctgcaa cagcgagcag agcgaaatcc 13500 acgcgccgag cagccagttg cttagctttt tcatgccaca actccgccag catccttgta 13560 cacctgaatc agcttatcca gtttctgctc gtgctgacca tagccagcgc ccggcaatga 13620 agcccagcgg gaacggcatt tatggatggc atcagcgacg cgaccagcct caatatcggc 13680 agtggccttg cattcgtgga ttagctgcat tgcaatagcg tcctgtgatg cgggggagaa 13740 gtcaggcaaa cgcagttgct ttttgtatgc atcatagaac ttagccagca cctgatagcg 13800 cccggcggca gtggatttga tacccagctt aggcaggcta atcagctttc gcgggtgatc 13860 ggaatagtcg gcaaacagtg agccaccaac aatcacatca tagccgtgat tattggtttt 13920 ctgccgccca ttatccgttc cctcgctgta cgccagcata tccagaaacg ccttcatgtt 13980 tttactaata gccataccag taaacctctt tttcagcctt gcgttttgct ttgttgtctg 14040 tcttctcgcc ccacacgatg aaatgcgcga cgacgcatga gaaacagcgg agattgtgtt 14100 tcttcagaag cgctgattta cggaacacgt caatgccgat atcggcggca aggcttgtta 14160 gcgcgtcgaa ctgattctgc gttgtctcag tggtgatgta aggagatatg tccacagcat 14220 caatgattcc aagcacctcc gcggcgcgct ccgatagttt cattctgcct cctgttcaaa 14280 taatgattaa ttctatcaca acaggtattg acgtagattg agcggtggtg catagtatct 14340 acatcaaatg atgcgtgagg taataaaaat gaatccacgt gatgttacgt tttacagtga 14400 gtcaaatccg aaggctgcaa aggttgccaa caaaaaagca aaggtgaagc aattgatggc 14460 tgccggtcac accaagaaag cagctcaacg catggtcaaa gaaatgaaat ggatgagtgc 14520 aaaatggtaa tggtcaaact caaagaaaac ggacgctgcg gagtattcaa ccttgaacaa 14580 atcaaaatcc gtccgtgcgg taaagtggtt gcgccatttg ggctggtgca gatgcgcgaa 14640 gttgagatta ttgagtacat taagtgaggt tgcatgaaag agtttaaagg aaccctgggg 14700 tcgtggcatt acgatgatga acttggtggg gtctatagta aaggcggcca attcgtgtgc 14760 gatgttaccg ataaggataa tgccaacctc atcgccgcag cgcctgagct tctggaggct 14820 ttgcagaaaa tgctcagcaa agcgtataag caaaactgga atgatgcata cccagaagag 14880 cttaaatcag cacaggatgc aatcaacaaa gcactgggag aatgaaatga aacttatcga 14940 cctgttagtt caagaattac ctaagcgtgg cgggtggcct cataatgctc tgtcaattac 15000 tcaagatgat gacggtttgc tgtgtgtatg ggacacgaat aatccacact atgatggatt 15060 ttcatggaaa catcacactg ggaatagcct tgtgtattac tggcatggaa ttgaggacgt 15120 acctttatct tgcgaccaca gggagtcgat agtgacctat tggcaatata aagcagcact 15180 cgccgcatcg caaaagccaa catggaacgg agaaggcgtc ccaccagtgg ggtgtgagtg 15240 tgagatatca ttttctggca aatcactagg gcagtgtgaa gttctttttg ttggtgattc 15300 acttattgtc tggaaacaga agtcatcaca gcaagaaggc agcggctacc acaggcatat 15360 gaacattcga ccactccgca cagaagcgga aaggaagcac gaggccgtgc tcgaatctat 15420 ctgcgcggta ttaacaatgg tagcgcaaga ttacaagcga gaggatgagg ccaaactcat 15480 ttatgaagcc atcgcagcag gcaaaattcc cggcgtgaaa ctggatgatt gatatgtggc 15540 ctatatgtaa gcattgcggg cgcatgtgcc ttacgagctg gtgcagaaaa tgcgataagc 15600 catcgaaata aaacaaagcc ctcacttaga gggctttttg tttgcggatt gccacgcttc 15660 tcgctgctta tcaagtcttt cctgtgacga ttcaagaatg acgggtttgc catccattaa 15720 cagtgttgga atttgggcac agtgacaatt atatttatta ccattctcgc tatagaacgt 15780 gtcaatctct tctggcgtgt aaaaccgtcc gtgtctcgct gcgtgtgtct ggcgagttgt 15840 gagcattaat gccgactgcc acagcatcac cgtctcaata cctaattcct cgcgcgcctc 15900 aatgacttct cgcctgttag cctgcctaag cgttccggtg atttcagtct gcgctatctg 15960 tttcgcgtag ctgtgagata catcgacacg cttaacgata tcatcttcaa tatcgcgagg 16020 gttagcgcca cgggcaatgc cttccatgat gactgatgcc agttgctggc gggaatagtc 16080 actcaatccg cgccaatcgg aatagccagc tgcataggca agttgaagcc tgttcaggta 16140 tggctcactg tagagtatcg cagcaatcgg cctctgttct gcataaaccg gagacaggct 16200 tgacagctct gaatttgcct tttgcgttcc ggcctgatac gcatcaccaa tgaacacgtt 16260 ggcccacatc ctgccgtgac cgaaatcatc accttcaaga agaatctcgt caatcagcgc 16320 ctgcaattca tccatgaagg aggctgcgcg cgcactactg aaatcgtaga aatacagacc 16380 gcttgattcg gagttggttt gaccatgcgg aatggtgcgg aacaactcaa gtgcacgact 16440 cctgagctgt ttgtatttgc gcgttatcac cttgtccatc tttgacaggc gagtcgcagc 16500 gcctaacgga tcattcaggc tctgcgatat gcgcggctgt ggaagtctag cgttaaaccg 16560 gagtatcttc attttcatct tccggaggtg tgtcttccat atatccatca ggcatttcta 16620 taggctcaag cccaagaaat cccctgattt catcatctgt aaggatttga ccgacaccag 16680 catttgccgc actttgtgca gcctgagcga gtttaacaat caattcagcc ttgtcgttct 16740 gcgttggttc aagaaggtca ttccacttgc aataatatcc agcgactggc gccttatcca 16800 caatgccaaa cgtgattaaa cgctcaacaa aagagccaac cagataatca agccagccat 16860 cacgtcgttg catagccatc attgccagtg actgctcatc attggctgat gcaagaacgc 16920 cgcttcgact tccaagcaat gagttaagag ggatattcac tgatgcggcg aactgactag 16980 ctgcaacata cataaatggc tcaggatcgc tcattgccgt tgacaggaca cttacgtcac 17040 tgccaaagct aaacattgcc gcgtcaatgc cagagttgag catttctata ttttcattta 17100 gcagatcggc aagctcctca acttcaacac tcatctgctg tgccaatgac tgagctgaga 17160 cgttatcttt attgaaagaa acgttcagtt ggcgcgatga gtttttgagt aatccctctg 17220 cggagctacc ggaaacctta gcgcaatcta tcagggagtt gaatccagcg cgaagtaaag 17280 gaacaccgct gaacatgctg ccgtcaaagc taccctctgc cagaataatt atgcggtcag 17340 ggtgaatctg cacggaacga tcaggcttgc cgtcactatc gaaatcttca acggcacttt 17400 cctgatattc gtacatctca ggcataccgt agtcttcgct ggcttcatca ttattccacg 17460 cactgacgcg gagttgctcc tcccacaccg gaataaagcg aacaatggat ttatctttaa 17520 tgcggcgagt tttggtgacg tctaccggct cattccactt acgcccatca cggatttgca 17580 gtattagcgc agaatatcgg ttaatcagat tccgcttatc tgcatccctg atgaatggaa 17640 gcgccttttt cagaatgtca ttgacgctct tttcccacgg tgaagtggct tcatcatcag 17700 cgtcattctc aagcactgta ggcataccat gccacgactt gttaagaacg atatttactg 17760 cggcatttgc cagcgggtaa cgttcataag caaaccggaa atcctcagcg ttaatttcct 17820 gcttgtaccc gcattccgtc cagagtctgt cgtgcttctg gtccagattc ttcccgccag 17880 cacaaagcct ttgttgctga atcgcccggt tattgttagc cacgcggtcg cgtatatagg 17940 cgtttaaagc gtcgagtttt gacatgattc accaataaaa aatccctcac gatggaggga 18000 ttatagcatg gatggtatat gtctaaacct tatacgggta tcgctttctg aactttccaa 18060 gcccgcaagt aacattgtat ggtatgcagt aaaaatgaac ctgatagcca cggccagcgg 18120 caacaacatt aactacggtt acgatttcgc ctctgtggtt tttatattta ccaccaacca 18180 tctcatctct gatggcgttt agtgtcctga agtgcatcac ttcacctcta tttgaaatat 18240 tgatacagca aacatggcac aacgccagtt accacagcga aaaatgaacc aaccataaag 18300 tgaatcaatc ttggttcatt cactccggca gccatagccc gccagaacat aaagttaagt 18360 ggaatcaaga gcgaccataa tagagccatc actccacctt ttcgaattta tcaaaaataa 18420 cagaaagatt aaaagcgcag ctttcagtga tcgcctggat ttctttcact tatgctctca 18480 tagcgtcctc atatgcaata actgcatcag ggccaattga taatccgcag aaactaccga 18540 cgctcgccac gcttccttgt cgctcaatgt gacagcaata aaaataaacg ctcatcactc 18600 aatctcccat cagttcatcg cgactatact gttttctcat attcctcttg gttactatca 18660 ttcttattgc agcaactatc ggcattgaaa cagggaaaga gatgagtagc agtaggcaca 18720 ataagccata aaccatgtct gccagcattt tcttatcaag aaaatcacca acagtctcct 18780 tcagccaacc gcaatatccc atcctgtatc tttgcttggt attcatcatc actcaatctc 18840 ctcatcatta acccagcttt gcaggacttc gataagctgc gcggcttgtt ttttatcaag 18900 ctgaacccag tcgtcacatt gccttaaatt gattactcgt tctgtattta tatacagact 18960 atggcattca tttgtttttt cgataaccat caaatcaccc tctcaaaaaa tcattcttgc 19020 agcagatacc cttgtatccg cgcttctctt gcaggttaac gaagacatca tccagagcgc 19080 gcagcaggaa gtcctcgtcg atatcatacc gacggcaaat cacatcatca ggcacaccag 19140 cccgcgccag tgaataaacc tgttcttttt cctcctgtgt aaatcctgca tagctgcgca 19200 tagtgatatc tcctttaagc ctgatgtaga ttatactatg cgctcggtgt agattggtca 19260 agtgtggtgg cgcagattta taaacattaa taataaatgt tgacatagat atgatgctgg 19320 tgtagattga actcatgaaa cgaaaggagt gaaatatgaa agatgttaag tttaacgcaa 19380 agaaaaataa atttggtcgc atcctgtttt atgttatgga ggacaacaag catctttatg 19440 agttcaacaa aatagaggat gcagcggaat ggattgctga acttggtcgc cgagcgttga 19500 ttaaatgaaa caaagccctc gattgagggc tttgttttta tcgcctgcgc cggattaaca 19560 tcccgctacc gcgctgaacg atgtggtcac caaggccata gcgcaaactg tcaatcgcgt 19620 gattgtattt atcaactatg tctgggagta tgttccctgt taatttatcc accttgtagc 19680 tgtacattgt catctcttca atgacgttct tgcatcttga gtgtacgtaa atcctgtcac 19740 acccacgcag ccacgtaata ccgtcctcaa tgctccccgg ccattttgcg cacggatgaa 19800 tgtcgaatcc agatcggcgt atatggctta ttgtttcagg ccttgcgcaa tccccatacc 19860 atctgtactt ctctgaattt ggaaatgctg atctcatcgc ttccggcgtg tcagttatct 19920 caaggccaac ctttgcaaag tcacgataga tatacaggtt tctgcgtcca tcgcccaaat 19980 cttctacata tgattctgtt gctgcggttg catcctgaga aaaaccaaag tcaatgccat 20040 aatatggccc tccccattcg ggagatggct cgaagtccag cgtttgccat ttcccgccaa 20100 gcacggcctc ttcggaacgc ttgttgaata acccttcata cacccacaga tagcgatcat 20160 aatccactgc cttcatctgg ttcatgtgct gtttaagttc ttcagtgaac cacgggttgt 20220 ggacgtagtt aacattaaca acaacaatgt catcatcctg atatatgcca tcgaccatct 20280 tgtcgatgta aggctcaaca aagttagtcc acgttgggtc agtctcttta ttcgggttaa 20340 aaacaataat aatttcagag ccagccgcac ggactgtcgg gattaatgta tcccatgaca 20400 cctgactgat attttctgat tcttcacaga atacatctgt aagaccagcc atacctttga 20460 tggcggttat gtttcgccac aggccgcgaa aaacaaactt tgacctcgtt gaatggtgcg 20520 ttatctcacc atcaacgcaa cggtattcct gagtgtggcc cttcctgttt atctcatcga 20580 ccagctctgc atagcttgat tctttgattg agttctgtat ctcacgaaaa caaccaacgc 20640 gactgttgcg gaaccttgcc ttttcgataa ggtaggatat acacgttcgg ctcttggaac 20700 tgcccctacc accataaaac accttaaagc gccgcgggta aaggataagc tccatccgct 20760 caggaattaa tattgttggc tcttcatcag tttcagatac accagtggct gtcatcttaa 20820 ggcgctttac gacattggga gaaccatcct gaagtagctt atctacaagc ccaaaaactg 20880 ctgattcagg ctttgcagtt gagttgccaa ctacctgttc aagtttttcg attgccacac 20940 ttgagagtct ttttctagcc atgattacaa aactccccgt gatgtttctc tctgaactcc 21000 gccacagctc tctcagcatc ttcttgtgat gaaaacctac ctaccgtata ttttttccca 21060 aaaaccctgc aatgcgcctt ccatttattt ttctctgcat cccaactcac accttttact 21120 cctgacgtat ttgtcgatgg tttaccaaca ttccatccgt tttcattatt acttgcttct 21180 ctcaggttgc agattctgtt atctgtcttc acgttattga tatgatctat tttcccattg 21240 ggccacacac cataaatgta aagccacgca agccgatgag ctttgtgtaa agacttatcg 21300 atgcgtatat ctatatagcc tgacttattc ttactgccag ctgaattacc aactcttacg 21360 ctttttgagg cgcgctgaac ccatgtgaaa acaccagtat ctggattgta atgcagtaga 21420 tgcttaagtc tttcctgagt gagagcgagc tcttttaatg atggcattct tgaatcctcg 21480 gttacaggcg gtctattgat tggatgcggc agcccggaga ccaatccggg cagggagcta 21540 ccctttgccg cattaattat tataaatcag ttactgttgt tgctccagca gtttctccag 21600 tcgctcaagg cgagcagcga gttcggtaac ttcggcaata tcaagaccag cctttataac 21660 ctcggcaaaa gtcttgccaa tgtccacagg tataacgcca gcagctatgc cacgaataac 21720 agcatcaatc ttctctaccg gagttccgtc atcagggaaa tcaacttcaa aaacaggggc 21780 gacaggctta ggtaacggac tgaatcgaac gataagttct ttcatcattg cggtgtcacg 21840 ttcaatcatc gccatctcaa cgatggtgtc atagagtttt tcctcgctaa accccttcct 21900 ttcaagagct tcaacgagca acttacgctt gtcttttccg cgtttatttt gtggttgatt 21960 ttctttactg aatagctttt tagccataga taaaacctat caatattccg ctatttttcc 22020 gttattcgat attgtaacag attctacacc atagggttaa tggcaaaaaa agaacccgca 22080 caaggagggt taaaggttgg gtgatgatat gagtgaaagc aatggtggtt attagcttat 22140 tgtacaccat cattaccacg cttgccagca tagcaccacg cattttctgt tcgcgtatgc 22200 acatgaacga tttcaagcgc atccgggaat gtctttgcta ccttcgcgat gaaatcgtcc 22260 agctggtgct gtttggcgat gtgccagacc ttttgcttag ttgtttgcat gctcaaaacc 22320 cctcgtagag cacatacact taatatcgtg aacaccatta tcaggaacaa cctcaatgta 22380 attacctatc tgcaccatca tgtagtggca cgtcttcatg ctgttccagt agcgttccca 22440 catgttttgc attgcgtcac tgatatcgtt aaacataatg caccactccc gcaatagctg 22500 ctaccagtgc cagcacataa acagcaagga agattttagc gccagtggtg tatcggcgtc 22560 gttggtttct ggtcatccat acatctccac taaaacgtgc gcacatagag cgcactgata 22620 attaatatga acgggtagct attcactttt agccaggctt tcgaattgct gtgctgtggt 22680 gtcaaactga accagactga caacatcgtc gaacatgaca aacccgccat cagggtcttc 22740 actcatgtca gcgccacaat cctgaccaca cgagtcgcaa ccaccagtat taagatcgta 22800 tcgcgtgagt tttgcgatat ttgataaatt cagcgccagt acagccaggt cataaacctc 22860 ttcggcggta taacctgcgc catgaccata catttcaatg cgggatatga tttcttctac 22920 tcgttgtttt gtgattgtca tttttgctca ccttcatgtt cttccagaaa aatacgcata 22980 gcataaagca tctcttcggt gtcatacggt gacaacttgt cacgcaggat gtgttcaatg 23040 ctgttaatga acctgcggat tgctttgttt tcgatttcag ccagggaagc atcggtgtct 23100 ggcgtttcag gtgcgtgcat aattgctacc accattgcgt catgcatgca gtcaatgtcg 23160 caacaaccaa cagcttcagc agttttgaac tcacgataca tattgctgaa cgcatctgtt 23220 ttgcaccatg cgtttatgtc cttaaatgct gcattctccg ctgccagcgc agcgcactta 23280 acttccaggg tcgcgtagtc ttcgtagtca acataatcac cacatggcga ttcgtaagac 23340 tcaacgccac caagtgaaac tctcatgtca taacgcttaa cttcactcat accctaaccc 23400 ccataatttc ttcgtaataa ccatctgatt gtcttgctgg catacatttt gttttgcaca 23460 aataagaact catatgtttt tacttttcca tctcaaacac catcggctct gcgattccag 23520 tcggagattg cctgttctgc agactccctg aagtttgtca ttctcgcccc gcatgagcat 23580 cgaatgagaa agtatggttt ttcatggtca gatgagcgcc atggcttaac ctttggttca 23640 ccaccacaaa acgggcattt ctttataatc aactcactca tatcatcacc atatacatag 23700 ctgaatcgtt tacaattcaa taaaacaaat caaagctgat agtttgcctg cccagatatg 23760 attaactcgt ccagcacgca tctatctcca tctctgtgcc atacgcgaca caccttagag 23820 catcttggag agctcactgc tcgctcaacc tgcttgctca taaagttttg cgcgccaacg 23880 tgaccgagtt cctgttccag cttttcgcgt cgatagatag tctttgccat ttgttacgcc 23940 tcgcatgaat taatgattgc cttaatgcgt ctacgatacc actgcattat gtgctcgtta 24000 tgccagttgc tcattttgtt actccttata ccctgatttt gaaacttcca ctgcgataat 24060 gatgaatgcc acgataacca gacttgctgc aagttcgaat gatgcgcctg tcatttacct 24120 aacccatacg ccgagattaa agcctgcatt gctgcgttcc agaatgcttc tgcaggaatg 24180 ctgttgtttg tgcgctcaac tgcgatacgt gccatagcct gtgcatcttc aaattcttca 24240 cggtctttta ttttcatatc ttcaccctcg tttgtttcga tgagtccaat atacatcaac 24300 gatgattcta cgtcaataca atgactaaaa caaaccaaac tgttagtgat aaccaacagt 24360 tattaatttt gtaagtaatt gatttttaac aggtgcattt atccgtttta tcccgctgat 24420 tttttcattt acccaaaaaa actcgtcata aatcatgatg ttgcgtagtt ttatcccatt 24480 tacacttatc ccgaatctaa tagagagaaa tataattttt ggaatggatt tttggtgaca 24540 aaaacatggt gagaaaaatg gtataaatcg gataaatagc agtatatata aatagtaata 24600 gtaataaata catatactta gcactaaaat tacttatccc aaactttccc cgttcttatc 24660 ccgttttatc ccgaattaca tttagcggat aagtgatttg cgcatgttgc ggcttggttg 24720 acatgggtaa tggataagaa taagatacct gatgtataag cgtgaggagg ttttaatgaa 24780 ggtaacaatg gcaactcaat ttgatatgga taatgcaaga aagagaacaa agtggccttt 24840 tagtaggatg aagcaaggag aaattgtttg tatatcagaa tgtgaataca gcaatacaaa 24900 ggttcagaga aaagcccatg cttatgggca tgcaacagga aaatcattca catgcaaatc 24960 aagtgatggg aaagtaatca tcaaaaggat ctcatgatgt cgataaaaac catttatgac 25020 ctgacggcag acataaacaa agaaaagtgg tacgacatta ccaaaccacc tggtcttgct 25080 ggtgaaattg ctgatgacat tgccgctggt gaggttcgtg aacaaccaag acttagagct 25140 gttgccgctc ttcatgaact gattattgcc agcaagggta agattaaaac accaagcggt 25200 atgaagggaa atcttcttac tatctgtatc gcagattcag ctgggggaaa ggataggtca 25260 caaagccatt tcaaaatcat ggcgagagat atcgaaaagg gtatgcatgt atttggtcgc 25320 attgcatcat caaaagatat cggtcggtca ctgataaatc atgatggcgt agcgacattt 25380 attattgatg aatgtcatgg attgtttggt gtaatgactc agaagaatgg cgcagcttac 25440 atggctgaac ttggttctga aattctgtct gtttattccg acagactgaa gaagttctcc 25500 gaccttgatg ctgttaacgc caaagagcag cttgagaagg aactcaagaa gctgaaggct 25560 gaagttaagg ataaagggat tgtagagtca gaataccgca ggcgcgagca gcagcttgag 25620 cgtgaaatat tgtggccaat tcagcagggt atcgaagacc cgatattctc aatgatgtgc 25680 ttttcaacac cagagaagct gtccagcatt atttgttcag aaaatatcgg aaccggcttg 25740 attggtcgag caatcttcat taaggggaag gacggtcgcg caaggaaatt acgcaaatat 25800 ggccataaaa caccacagtc tctaatagat aaaatgaagg cagtggaaaa atcatcacca 25860 caggttgcaa gatacgaaaa tgatgttgtg caggcgcttg ctgaatcact tgatgacaga 25920 tttgaggagc tggtaaatga tgtttctctt ggcgcggtaa ttgcccgttc attcgagcag 25980 gttgaaaaag ttgcaactgc actttctgct gggaataaag gtgtaattac agaagaaatg 26040 ctgatgtggt cattctgttt tgtttgcgaa agcctgacag acgtcatgag catgctaaaa 26100 gtgaacgaaa gccaggaaga actcggaaca atggccagat ggaatgagat taaaaataga 26160 attgagaata tcctttctgg aagaacgaag gatgacagga tgcctcagtc tattctcgtt 26220 cagagggctg ttaaaacaaa atccctcaag gctcttgctg aggctatagc aaggtctaat 26280 ggggaagatt tttcctatgg ggcaaaaact cttgttactc cagtaataca atctctcatg 26340 gcatctcgtg caattgacgc tgtaggttgc ggttactgga ttaacgacgc aagtaaattt 26400 gaaggtacga aaatgagcgt taaattcacg caaattgttg atggtattgg catgaatatg 26460 gctgcaatga ggggttggcg atgaatatag tgattaatga aaatgttgtt aactgttatg 26520 caacagaaac tcgtcctggt aaagttgatt tcacattggg agctgcggat tgtgattggt 26580 ttcatgatct gtttttccca tatggagact ctcaagaagg cattgaagtt attggcggta 26640 ttttttgctt caaagacgtg catggtaatg gttggagagg cgtcttgatt ggcatagatg 26700 gacatcatac tggtaaaaag tatcagattc acacgtctgg aatcggggaa acaaaagaca 26760 aggcagtaaa aaacacaagg aaattgtggc ttcgtatacg gaatgaaatt gagcataaac 26820 gcaatgaggg tgtgctttga tgagcgccaa taaaaaactc aagtttctta ttcacaaggc 26880 gatagctcta aagttgtatg aacatcgact ttttcttctt gagtgttcag tatctccttg 26940 tggatatggt gattatgatt actccatttg cattggtgaa cgccgtggat ggtttgagac 27000 gtttaatact ctaagtgttg gtaatgattg cgagaaaata aataattgct tgtgctggag 27060 ttgcggcgat ggtcttttta gggctgttta catagataca ttttgtaaga tgggagacat 27120 aatcctgtat tcaacagcta caggtggttc aaaagacaga gcttcgcttg atgccattta 27180 tgcatggagg aatgcaaagc gagagataat aaagattatt gacgatgaaa ttgacaagat 27240 gaaactctga taacaaaaac cctccagtcg gagggttttc ttttatctgc tgactgacat 27300 tttctctatc aactcgccag cgtcataaat ctttcttctg attctcttcg ccatcctgat 27360 tgtgtctgca tcatcaggca gcatcaccgg aagtcctgcg ttttccgcag cgcaaagttc 27420 gtcaaattta taattaacta tgcagcgtaa ccgtgctttc gtctcatcgc taacagaacg 27480 caccacttcc cacatgtttt ccggcgacca gcagcaccag acatgcgcac cagtgaagta 27540 atggcatttc cacgcatcgg cataatcaga taccaggtaa atgaactttc cattgtcttc 27600 tccgattgaa cttatcgcgc cgcgagtgag tttgccgttg atggttgagt ccttgttgta 27660 tcctgcgcgg aaaaacgctc tgaatgaatc accatccatg ccaatgaatg ccacgttgca 27720 cggcttcatt gtgtcagcgc gcatcatctc aaccgcaata agctctccag atttacctct 27780 ggcgacatta acgtcgcaac caataccatt tatcaatgtc cactcattca tcgctacacg 27840 cgtagtttta gccatgattg cggcgacttc ctgctcagtg atgaagtcat cgttgtgatt 27900 tatcttcggt agctctttcc tgattgcatc cagcttttcg cgtgggttca tgttcaggaa 27960 tccactaagc gcctccagtg cttcaggaaa actcatgccg gagagtttca ttagccaggt 28020 gattccgctg ccgctgccgc actggttgca tattgcgcca ccatctcctt ttgtttcgaa 28080 gttatcatca aaacgatacc tgtctttgcc aaggcatgat gggcacggct ggtgctttcc 28140 attgaaaacc ttgctgtcca cattgacgat ggacatgatg gcagcctgcc agttgccgag 28200 catttttggc tcgatttctt tccagtcgta tctcataaaa tcttcctgtt gacgatgatg 28260 tagaatcatt gtaatttacc tacatgaaac aatcaatcgt tacttgcaat gaaacaatta 28320 atcgttacaa tagaggataa gaaatggcta tcaccgttaa gaagtgcgag gtttgcggaa 28380 atgagtttat cggaactgca aaagcaaaat gttgctcagg aaagtgtaga ttgcgcaagc 28440 acagacagaa gaaaaaccca attcataact caaaaacaga taatggaata tcttgaatat 28500 aaccccgaga ctggcgtctt tacagctgca aaaacacatg gaacactctg gcgtaaaggc 28560 aaggttgttg ggcataagaa taaggcaggg tacattacca tcacgctact agggaaacta 28620 aggaaagctc ataggctggc atggatttat gtttatggag aagatattga tgggtatgaa 28680 atagaccata taaatggtga caaatcagac aatagaattt gcaaccttag gatttctagt 28740 caccaacaaa acatgttcaa catgaaaaag aaatcaacaa ataaatctgg tgtaaaaggt 28800 gtgcatttcg ataaaagatg caacaaatgg agagcgcaga catcaataaa caagaagagg 28860 gttcatcttg gtttgtttga caccatagaa tcagcagaaa aggcgattcg tgaattcatg 28920 gttgctaacc ataaagagtt tattaattta gggtgagtta tgcataaaat agacaaaatg 28980 atttcagaga ttgatattaa tctgctgaaa tcctatctgg atactggtga tatcgagcca 29040 aggccctatc agtggttgat atataagtta actggtgatg tgattcgtca ttatgttggc 29100 cctggctatg taacagcaag cgtcggtagc ggaaagtcac tgatgattgc catgatagca 29160 aagcgttttc aggaaattgg ctattcaggg atgattttat caagacaggg cgaaatagtg 29220 gagcaagatg cggaagagct atggtcgctt ggtgtaagaa actcgctatt cagcgcttcg 29280 ttggggagga aaagttctac gtatccaata atttgtggtt ctgagggtac tgttgtaaat 29340 gctttgtttg ataaaaagga tgaatcaggg aatgttattg caaaaggtgc gctttctgac 29400 ttttgcccga gatttctgct gatagacgaa aatcatatgg ttaatgacat tgatgttgtt 29460 aatgatggtg atacgcagta tgcagtgata attaatgagc taatgaaaag gtgcaaagat 29520 aagtacggcc atgagttgag aataataggt tatacaggct caccgttccg cggcactaca 29580 tcaataaaag gtgctttctg gaagaaagag attatcaata tagacaccaa gtacatggtt 29640 gaaaacggtt ttcttgtgcc aacaattttt ggtcttcatg atgttgacag tctgcattat 29700 gacctttctg attttcatgg ttcagatgtt gatggtactc aggattttac caccgagcag 29760 ctcaagcaga tgcagaaaga aatccttgag caaggaactc ttacacagaa aatcatgctt 29820 aaagtgatgg agcttactaa aaacagaaac ggagtattga ttacatgtgc tggcaagaag 29880 cactgtcagg aggcggcaaa atacctacct gaaggaagct attcaatagt tacagaagat 29940 atggggccaa aagccagaag gaaggctcta aaagatgcat acaccgggcg caaaaaattc 30000 acattccaga tagcggccct taccactggt gtcaacattc cgctatggga tacgagctgc 30060 atattacgaa aaataatgtc gctaactctc cttgtccagc ttcttggtcg cgggatgcgc 30120 ttgctgaaga aagagcaaat tgacgccggg tatcataaag aagaccatct ggttctggat 30180 ttctcaggca cgatgtttga gcttggtcag ctgtatgaag acccgattct tgaagaggct 30240 gaggcgcaac gttcaaaacg cagtggtgaa caggttccgt gcccgaaatg cggaacgatg 30300 aacagtccat atgcgcgtcg ctgcattggc aaagatgcat tgtcgccaga tggtcgctgc 30360 gaagagtttt tcagttatat ccgttgcggt ttcgataagc acggaatcag aatttttgat 30420 gatggttgcg gcactaaaaa cgaccctaca gctcgctatt gccgacattg cgatcacgtt 30480 ttgcgcgacc ctaacgcggc gttgaatgag cgtgcgtata cggataatga gtgggctgat 30540 gttatggatt tcaaagttca gttaacgaag gatggagagg ggattttata tcgctactgg 30600 attaatcgtt gcgatggcaa agaaggatgg gctaacgaag tattctatcc atacggcggc 30660 gcgactcaca tgaaaaacat gttcaaggca aaggctatat tccctcacct tgatgataaa 30720 tcaatggctg gaaaaatcct gaagtgccag aacgccaagc aattcatgat gtatgcagga 30780 ttgattaaag cgccaaagcg catcacgcat cgcattaatg ataaaggtcg agacatcatc 30840 caccgaaaag actttaaagg agagcaaagt gaagcggctt gacagcggta tatgggtatt 30900 cgatagcggt tatcgcggag aatgtccgaa agaggagata gaccagatgg gttacggaac 30960 atggatgcaa catcgcttcc ctgatgttct gtggtttcat gtgcctaatg aaactggcac 31020 atcaagcagg gtgcagtttg tactgaagcg ccagaagatg ggggttaaga ctggaatagg 31080 cgataatgtg ataatgactc cgggggtgaa acacagttgc ggaatgattg aggcaaaacg 31140 ccgcgacaaa agtaagagca gggttagcaa ggagcaatcg gctgtgttaa ctgagatgtg 31200 cagtcttggt cattatgctg ccatcgctta tggacttgat gaactaaaaa aagccacact 31260 tttctatttt ggcttgcctt ttgatgtgga ttgatgtaga ttcaactaac aataacaagc 31320 gaggtgatga agatggatat tgagattccg gatagttttg atgctgagtg gcaatgcgaa 31380 atgctacgca atcttcttgt taagttaaac gaacttgatg atggcggtca tgttgtcagt 31440 gatggctatt cattgcttga tgatgcaatg aaaattgtcg aagcgttacg tgaatacagt 31500 ggtgattaaa tgagagtcta tttcaataat gaattaacca atgagcaata ccacgccgac 31560 acagagtaca ttaatggctc tggtttgtgg aacatttatg accgctgtcc cgcagcatgg 31620 cgctacaaag acgaagagga tgagcagtca aatgccctca ttttcggcac aggaagccac 31680 acagctctgc ttgaacctga acgtttcgat gctgaatatg ctcgtatgcc aacaaaagaa 31740 gattttggtg atgacctgct tgttactgcc agtgacatga attcatgggc aaaagaacga 31800 ggaatcaaag gactttcagg gaagtcgaaa gctgaggtga tcaaaatcat ccaggcgact 31860 ggcgagccag tgaaaattta cgatgtcatc cgtgaagagg ctgaaaaagc tgctgtagga 31920 aagcaaatgc tggaaggtgg tgattatgac gccattcagc aaatgcgtgc tgtaatccac 31980 gcagacccat actttaagag tgttttcact ggtggttact ctgaagtttc aatacttgga 32040 gaactaatgg gtgaaccatc aaaggttaga tatgattatt tatctactgg agctgatgtt 32100 tgggattaca aaacagccat aagttcaaag cctgaagagt ttttccggca tgctgcgcga 32160 cttggttact ttatgaagat ggcgatgcag cacgacatgt ttgttgaggc atatggtcac 32220 cctccgcgct cagttaatct tctggtacaa gagaaagcag ctccgtatat acatacaggg 32280 attagacttt cagatgagca attacagatt ggtcgcatcc aattgagaaa tgctatggaa 32340 atttacaaag catgcaaaaa agccaattcg tggccgggtt attcaatggg taatccagtt 32400 atagaaatgg aaacgcctga atggttcaag aagcaattta atttataatt agtgaggtga 32460 tgcaatgggc attctcaaca ttaaaccagc agagcgttcc ggttctcgcg tggtcatcgg 32520 tatttcaggc cagtctggta gcgggaaaac atatagcgca cttaagctgg cacgaggcat 32580 ggttgattca ccagaagaaa tcggattcct tgacactgaa aacggtcgcg gtcgcctgta 32640 ttcaaacatc cttgatggta aattcctgca cgctaatatg tatgcaccat tcagtcctgc 32700 tcgttaccgt caggcaattg aagagtttca ggccgctggc gttaaggttc ttgttattga 32760 ttcaggctcg cacgaatggg aaggggaagg aagttgcacg gagattgctg aaaagcctct 32820 gcttaatggc aaaaagatgg ctgactggaa gcgcgccaaa gctgaacaca agaagttcat 32880 gaatgccatg ctgcaaagca atatgcatat cattgtatgt ctacgcgctc gccagaaaac 32940 cgacttcgca aacccgaagg aacctgtatc acttgggttg cagccagtgt gcgagaaaga 33000 cttcatgttc gaaatgactg tgagcatgat gatgcacgat ggcggtaaaa ttcaggaatt 33060 cactaaatta ccagaagaac tacgcccaat attctttgag tctggtcggg aaagcgttcg 33120 acatggatac attggcgaag cgcacggtcg cggactcatc aagtgggtgg actctggcgt 33180 taaagttgac gaagagtttg aatcttggcg ttcacgactt cagctttccg ccgcaaaagg 33240 catggaagga ttgaaggaag aagcaaaatc aatacctgat aacctgaaag ataaaattcg 33300 cgcaatctgg ccttctctcg ctgcttctgc tgcagaatac gatcgcattg agtctttcat 33360 taatgatgag caattaccac aggtggtaat cactcctcag gataatttcg accctgcaaa 33420 actggctaaa ccgaaaccac aacagccaga accgcaggaa gaaacaaaaa ccgaacataa 33480 accaactcca attgaaggat tttaataaat ggcacgcggc gtaaacaaag taattattgt 33540 cggcactctc ggaaacgacc ctgaagttaa atatgcagca tcaggctctg caattgccaa 33600 cctttccgtt gcaacatctg agcagtggaa agacaagcaa acaggagaaa agaaagagca 33660 gactgaatgg catcgcgtgg tcatcttcgg aaaacttgca gaagttgcag gagaatacct 33720 tcgaaaaggc tcgcaggttt atatcgaggg acagcttcgc actcgtaagt ggactgacag 33780 caacggcgta gaccgatata ccactgagat tttcattcca cagatgggcg gagttatgca 33840 gatgcttggc ggtaaacgtg atgattctgg ccagcaacca caccagcaat caggacaaca 33900 accgcaacgg caacagaaac caacaaaaca acaaagccca caaggaggca atgagcctcc 33960 tatggatttt gatgattcaa taccgttctg atgataaaac taaccccgcc gaagcggggt 34020 tttacactat aatcacacag ttgctaatgt aaccctaact aaagaaccat cagctttctt 34080 gacaagtgct tttagtgagc ttccttccca gtatggaacg aagcaagagt tatcttttac 34140 tgcgctatcg ctaacgacgg ttgggctgaa aggtatttct gctgccctgt tgtctgtgta 34200 gttaaccttt attgatacgg catcactaac acttccagac gcagccccca aagacgccca 34260 tgccgaccca cttccagcgc catttgaatg tgccttaata ctaacggcat ccattgtagt 34320 gctcagctta tgcagcctga tatctaatat gccagtatct tggtaactgt taatcctgga 34380 attccccagc attgggtcaa caatgttagc agcattaacc tttctactgt caacattacc 34440 agtaatacct gatattgtag tgtttggcgc gtctactatc agtccgttag atggggttgg 34500 ctttatacca actaaacgca aaccattaac aatacaatct ccttgtatgt atacctgatt 34560 tgcattgaaa tccagcgtat ttgtatctat tactgaaaca ttggtgaatg tctttccata 34620 tgtaaaccat agtgctccag agcctgcgca atcttgcatc aagacgtttg atacatagcc 34680 gcctttacca tccattccta tgccaacacc tagtgagcca atagctacaa ggtcatcaat 34740 tatgtggttg gtcggtaatt gatgtactgg atactcagcc aacgtataat cacctggcct 34800 gtcagtttca ttgccgatat cagcgcctaa atcaaaccca tcccacacag ggtacattga 34860 taatgatttt ctaaactgaa gattgtaaca acgggcagat gtacttccga ccgttccctg 34920 ccatgtctta acacctgact ccccaggacg gaatgacgta aaacctataa caccgccatc 34980 atggtcaacc ccgccatctt ggcgcaggaa ttgaactgag ctaacagaac cgtaagcaat 35040 tctcccacct atacagtagt taccaacccc cttattaccg gatagattca taaaggtaat 35100 tcccgcatcc ccacctgcta ccgccaaatc agaatcaaca gctttacaat aaaagcaagt 35160 atcaaacagg tagcaaccga ccgacccttt agcatttttt acagtaatac cagtacagtt 35220 aaaaatacga agtgtggaat ggatatgttg gtctttcgca taactaggca gcaatgcctc 35280 aattccagga aatttggtgt agtcgcttac ggttggttga taacccctat ccctggtttg 35340 tgccagcgtt gccgcaactg ccgcggcctc cgtaatccaa cttccatctc cattccatgg 35400 aaaaatcatc cacggagttg tggcactttc catatacgga gagtttacta aagaacccgc 35460 gccaagatta gtaaatgtaa gattaccatc tccgataaat ttagctttac agtcgatggt 35520 tagtactttg ccgccaaaat caactgtctc gttgtcggtg aatgtatagt cgcggtcaat 35580 caacactccg tcaactgctg ctgttgctgc ttcctgcaag gtagaataat ctgataattt 35640 tactgaatat ttgaattttt tgttggcttc ctgtctaaat gctgcgtcac caacactaat 35700 ccacgcgcct aaaccaacgc caccagttga tgcaggagtt gaaccagcag ctacagcctt 35760 aggaaatgca ccatcccatc ggtaatattc tccggttgcc tcgtaacgta gcacctgatt 35820 tggtagcgtc aacgtcgcgc catcttcaaa gctatccatt gtgatatatc cataagcacg 35880 aatggcctct tccgcagtgt actggaatcc agcaatagtc cagcgtttta cgccaaatct 35940 gtccacatag taatgtgcat cagatgtcat gacttcatca aatttaccag cgttaaactt 36000 caggtcgcgc gggtcttctg acgggattgg taagctagtc ggtgtggtag ccattataat 36060 aaatgctcct ttgtgaattt gatgtatatt gtatcacgat gacgggatga catattcgta 36120 catgtcatca ctgtattcgc tcatggtcag agttgttgta ccgtcacttc ctggattttt 36180 ctggctgaca acccacagag tggtatccag ttctttttca gtgctcagca catagcgaga 36240 ttcagattgc acgcttgctc catcccatat attcagctgg aaatcagtcg gcaggttgca 36300 ggtgaatgta tgcaatccgg tcactgttgc tggtaatctg tctgatgtgc tgccatcaga 36360 actggtaatc acaacataaa gattatcatc agccgttagt tgctcgcttg ttgtgaatac 36420 gtttccgttg cgcgcttcaa taacgccagt ctgttgcaca tcatcataca tatcgacaac 36480 ctgaatcatg tcaccaacgt tcacatattc cccatccgaa agagccttaa tctccatgct 36540 acgacgggag taaatcaggc ggcgacactc aaggattgcc ctgtcaacag cctgatatcg 36600 attgcgaaca taaagcatgt cgaatttctt ggctttcgtt ggttcgcctt cgactattcc 36660 gctatcggta attcggtagt aaacgttggc ttgcttattc gttgttgggt cgcggtattc 36720 gacgttaacc ccgtcataag tccctggaag gctgatgtcg taacttaact tgtatccgtc 36780 gctctgcgtg tttctggtgt taaatactgt tgctggatat tctcgtttct catcacgcga 36840 aaagctcatc acgccatcat cccagaatgc ggtgactcgt gctgcgtcgc agattgtttg 36900 caggcgttcg ccaatacttt tatcttcatc atcgaatgta tagtcgaaac aaccaagtcg 36960 ctcatcaggc aggctgtcgg caatttcata cagcttcact atgtcgattg tgttttctgg 37020 attgccagcg gtaataagcc agttatgcag cgctgcatct gcaaagctac gggaaggtgc 37080 aagcgtgtag cgcaccgttc cagtatcacg gttgtatccg atggtgtggc gcgtgattag 37140 cgcattatat ttcctgtcac ggctgcctgt tgcgttctct gtggcgcgca caacaacctt 37200 aaccacagtg tcatctggat atgagacgtt tgttctcgtg acgattgagt gaacctcctc 37260 aagctgaaga attgaagtgt cggaactgtt gtttgtccgt cgcatctgga tcgcgtagcg 37320 accagtacca gcagatggtg ttaacttgat cgtgtagtag aacgtatcat ttctgtccac 37380 gtcctgataa tagttcatcg actgatatgt cccgggaatc tgaacgttat catcgtcaat 37440 cttccaccac tcaatgagta cgctgaaatc attgccatca ttggtctggt gttgcaggtg 37500 aacccaaagc tgatcacctt caattggcga gaaatacgga ccagaaacaa tcggctggtt 37560 gtctgtcagg ttgaaatagg tattattaat cgtcacgcca tttagagatg atatcggcgc 37620 gcctgagtag ttgatattat ttataataaa tgtgtaccag tattgggttg gcggtaaccc 37680 tccatcgtct gtttctgttg cagatataag acgaccagac attgttatgt tttcagttac 37740 agatgcacca cctccctgcg cgtaagtgat attcagtttg aacaccacat catgcggcat 37800 ggtaaggtca acgaaataat caaacgccga atccttcggt atcttgactg ctatctggcc 37860 accagcaaat tctgtctccg tgactgtagt ggttgttgca gtctcaataa ccactggcgg 37920 tgggtcggta tccagttcgt ttggcccgta cagttcctgc ccatcaacat catcaaaagc 37980 ataaggctca tacacaacag ggatgacctc ccctggctga taaatagtgt aacttgcacc 38040 agcaagtgag ccgaggtttg actcggagta acgcacagaa gatacatcat acttgccgag 38100 gccaaagttc atgaactcgg tcacgtactt gatattgttt acatattcaa acaatgattc 38160 ctgaagcaaa tcagggaacg cgcgaatctg cccgaagtta tcagggcgcg cctcaccatt 38220 tcgcgcaatg tttgtctgtg ctttcaggct ggtgttaggt gatgttttgg agctggtgtc 38280 cgtttttggc gtggatacct tcggtgtaag gaaggagaaa atcttcgtta ctggcttcag 38340 tatcgagctg ataaggtcgc caattgcgcc ggatggctgg caataaatgt tgacaacgtc 38400 gccatctctc aagcagaaga aaagctcatc atcttcacca agcactctac catttaccgc 38460 aattgaaatg ctggctggca ggtttgattt attcagccac ttccacaggt tagtgcccgc 38520 tggcacaatt cccgtctctt tcggcgttcc cggcatcttc tgaacatgaa ttactggcat 38580 aggtgagaaa ccttaacttt gttgatattt tttcgagtgt tcgcagcctg tcgaatctga 38640 ctgccgtttt ctctcgcgca tgaagtattc tatcacggcc ccatatcatg gcgatgtgta 38700 ccggaacgtt gccgcgatat gccacgacaa catcgccagt tactggtgat tgcgtgtcct 38760 tccagaacgt cacctcgcta tcgaaacagg taacaaaagc gccgccattg tcgtagctat 38820 cgtcatgatg aatattgatg ccacggcaca ggcggtaata aagaaccacc agcccccagc 38880 aatcaacggc gtcaacatgg caacatctgt ccttgtacgg cttgccaaac attaactgcg 38940 caaattcttc atcagacatt acgcagcccg gggaattgag cgatgtcata aagttttgcc 39000 acgtttcctt tgattgggtt tttgattgac agggtcacgg taacgtcaga accatccatt 39060 gccacatcgc tgacatacag gcgatatggc ttcagtggtg tgtttgtgtc agtttcttca 39120 aatcgctgat acagtgcgct gattggctca atacgaccgg aaccagtcca caatttaagg 39180 tattgcttga aatcattcgc cagacgtgca aacttgacgg ttgcgttaat ggctggagtg 39240 ttcgactgct gagactgtgt gatgtccatg cgcactggca gataagtttc accgccaagc 39300 actatctcat ccagcacgtt agccacaagc cgcacataac caaaagacga gtggtaaaac 39360 gttatcgtgt cgaataacgc ccagttaggg cgctttgctt tgtaatcgcg taatgatggc 39420 attattgata ctccagcagg tcacggttaa cgacttcatc cagccatcca aaccatctgt 39480 aatccagttc aaccagaaca tcatcaaact catccatcgt gttattgagt ttcttagcga 39540 taacattgcc agtccatgtg accacgccgc catcaatgct ggtttgcaca ggataatcgg 39600 taaagtgcag cgtctgctcc tgtaatccgc tgccgccgag gtcaatcatc atggtgaacc 39660 agttgttaca cttattcagg tagcgtgagc tacgcaacca ctggataaac gctcgttctt 39720 ccgccagcgt aaaaacccac gtcaggctcc atgttactgc gacgtcagtc gttaattttt 39780 gaaatattgg tgccccaacg gctggggtat ccttcctgaa aggggtttga aacgtaaggt 39840 ttttgctagc tctttgcgcc aaaggcagcc agtcagggta tttgactatc atgtggaatc 39900 ctctttgctt tgttgatgta ttttagcacg gcgcaagttt caccactcca tcatgagctg 39960 gtttaaaatg cattcgttcc atgatgtttt gccatctaaa atagcttgca aaaattctac 40020 atttgaatgt agaatttaat tgtcacatta aacaggagaa ataatcatga aactgcaaac 40080 attagagttc ccgtacggag agatcacttt cgaccgtgaa aattttatta acgttaatga 40140 gcttgttaac cagatgaacc gctggagact ggataatggg atggggacaa gagaaatacg 40200 acaggtaatg gcaactgatg catttaagga tttcaaggct gagtgcgaaa agcaacttgg 40260 tatcgatagc gcaataaaat caacgcgagg caggaatggt tccacttttg cttgcttgca 40320 tctggctgta tatatagcag agcaatacag cacatatttc catttccttg tcatcgaccg 40380 attcattacg cagagacagg ttgagttgcg aaatattggt gcggtaagtt tcgtggaact 40440 taatgctgcc gtcagcagaa tgcttgaacg cactgagggt agaattggtc atagtgggca 40500 tttcattcag gtggcaaagt cagtcaagga gtcgatagat atccgtgaag ttactgggtt 40560 tgacacatgg gactctcagg atgcaaaaac taaccagtta cgcagtgata tccagaagtc 40620 tcttgtcaca cttctggata tggaagcggt caactcatgg gatgaactga aagaaacgat 40680 accgagggtc gtacgtaaat gcgctgataa gatttaaaac aaagccccat aaggggcttc 40740 tttttactct gttgctcgtc tgttggtgtt gtagtttctt gagatggctt gccctattgg 40800 gccattttcc gaaatatcac tcacaatcgt ctcaattgtc acgctgccgt ccccattatc 40860 tctggcgctg ctgctaacct gcgctgagct gttgttgata acgctattat aaaccacaac 40920 accgccacct ccgccggaaa tatccttatt gctgataacc tttcctgagt tgccagggat 40980 catgtattgc ctgcctgtgc tcgcctggaa tatttctggt gcatttccct cgcccacttc 41040 atacatgctt cctgcgctaa cagggccgcc attcttgcgc ttgccagcaa tacccatcgc 41100 cagtgcccca aggacagcgc ctacaccaat tgcagctgcg ccgccgaatg aaccgattga 41160 cgcaacgatt gcagcggggg tccatgccgc cgtcgtggtg gctgcagccg cagtggaggc 41220 agctgtggtg gttgccagtc ctgccgtttg cgccgccgtt gtggtagcgg ttgctgctac 41280 ctgagctgtc tgccccataa ccgcagattt cacccactgc acgcccattt caacaaagct 41340 gtttaccaga gaattcagca ccgtagagcc gaggctgcgc atggcatcct gaacgctcat 41400 tgtgcctgtc agtaatccgg taatgctgtt tgacgctgtg ctcatcgctg aatcaagagc 41460 agtgccgaac agttgcgctc cgaggctttg ttgctgccat tcagcccaca ttgcatccat 41520 tctctgctgg cgatattgcg cttcaattgc tgcgcgagtc tgttcaatct ccgtgatttt 41580 ttgcggatat gctgcggcgt aggcatcaag gtcagccatg cgttgctggt attcactgtc 41640 aatgccagtc gttggtgacg caatggcacg caatccctga tatgatttct ctacgcgctg 41700 cttttccttc tccgcttccg cctgttcctt cagcgcattc ttctggtccc aaatcttcgc 41760 agcgtactcg ccagccagtt ttatttgctc ctgagtggct gccttgccaa gcgattgctg 41820 cgcgttgaga attgcttgct cgcgtgatag ttcgctggta gacgtggcat tgagcatggt 41880 ttgctggcgt aatttctcca gcttctgtga caccgattcc tcaaggtttg cttgttttgt 41940 cgatgcagct atgcgttttt tatcttgctt ttcctgctct ttttttgcgg caagttcagc 42000 tttgtaagcc tctattttgt cgaatgacgc attgattgtc tgcttatccg catcacttgc 42060 cccaagctgc tctgccctgt atatcgcttt ttgtctggcg gtgaaggcaa ttgtttcccc 42120 ttcctccttg attgactgga tataagcctg aagccttttt gtgttttctt cagtggctct 42180 cgcatcctct tctgaagcta ctttgtgccc gttcagcata tcagtagcca tctttgtaga 42240 ttctgctgcc tgatctgccg aaatggaata ttcgccaacc ttgccagtca gttcagatag 42300 agacttgttt gcatatccat atttctgact aaggtcaaca gtcaggtctc gtaattctgc 42360 tattgtttca ggattggcgt tttttctcac cgccgccaga gcttcaacca gcttcaaagc 42420 atcctcggcg cttatgccaa actcatctgc cagacttttt accacctgat taagctggtt 42480 tagtccgaga atattaccct catatgtccc gccaagattc ttgagtgctg tgtttacatc 42540 aattcctctt gctttcagtg tgtcaagctg gctgatggcg gcggatagtg gcgctttcca 42600 tgagccaagt gcgtcgccaa gctcattgac gccctgtact gaagccttga tgatgttgtt 42660 tgcatcaatt agagccattg ttaactgtgc tcttgcggcg ttttctgact gcttagccag 42720 tgttgcaaat ttgtcagaga gaaccacaac accattagca gaaagctgga atatgtcggc 42780 aagacgctgt tgtgcggcgg tcagtgcctt tgtggaaaca gctgcgttat ccatgccagc 42840 aattaatgag ccaacgatta ccgtaccgat ggttagcaat gcaccggcaa ctgcgcctcc 42900 agaaccaaag acgcttaata actgactacc ttgttgactt aaagcaacga gtgccgattg 42960 tccgctctgc acctgaacta caaagtcctg aatctggtag ccgccctgtc tcatggcgtt 43020 atttaaactg gagaaactcc tgccagattt ctcagctgtc gatgcggtgt tttttagccc 43080 tgtgtcaagt ttatttatcc cggcaattga ctcatcaatt gacttctcaa tctcctgaag 43140 aaccttgttt accttttgcc cgccagtagt cagcccggat acatccatcc cgacttcata 43200 aacaattccg ccgacttctt cagccattat gtattcctcg cttttttcgc tttgcgttca 43260 gccagtgcct tcatgcgctc acggtctgct ttagcctgat cgtactcagc cgcacgttct 43320 tctttcgtta accctttcgg ctctggatat ttattcttaa tcatcatctg aaactctgtc 43380 atggacaggt tttcggcctc atctcgcgtc atgtcgaagt gcgtgcgcgc tgagatgatg 43440 tattgcgacg catgaaactc gtttgtggtt ttcttgctct gctcttccag acgctcaggc 43500 actttgagtg gtgacttacc gatgatgcca tgctgcatca ggttgcgcgc aataataata 43560 atgtcgttca ctggcatgat gccaggcacg tatcgcacgc cacgcggagt tggcttccat 43620 ccgccaatca gcacagaaat atcatcttca cagcatgact gcatgacgat ataggccgca 43680 ctcagcacat ggcgaccata cactggcttg ctgatggttt tcatgacttg catctgcgca 43740 ccaaatggca ggcactcgac gtgctgcagc ggcgtaacat aatcaatgcc attgagctta 43800 gcgtacacct ctacaatttc ttttggcgtg ccgatggagt tcatggcgcg gaatgatggc 43860 ttaaagaaaa aactcctgtc ggaaagcgag atgcgcatct ctccgatttc tgttagtggc 43920 gtgcgattgc tcatgttttg catcctgaat ttgactgatg ttgattatat catctcagtg 43980 gtgttgacac ctgctaggtg gtgatgtaga ttcaagtcat cgaaacgagt gatgaataaa 44040 tgaggtgagt tatgaaaatt aaaacgttga ttgcatcagt gctatttgct tcctcctttg 44100 cggtaagcgc aacctctgag gtttgcaaaa acatcggaga aatcgccatg aacactgccg 44160 atgctcgcga taacggtatt agcaagaatc ttgccgaggt ggtagtaaaa ggctcagcaa 44220 aaaacaacga atcagcagaa ataatcggcc ttgctatcgt agaaatggtt tatgcacgca 44280 aggatatgac taaagagcaa ttgcgtgatg tggctgttgc tttgtgcgaa aagaatggca 44340 tgtaatataa acaagttatt aacagttgag gttagttatg gacgttgtta ttttgttgtt 44400 ttttgttggt ttggtgatat ttgcgtacct catgccatct tttgtggctc tgcaacgcaa 44460 gcacgtaaac acgactgcaa tctgcgtact gaatattctt gttggatgga gttttattgg 44520 ctgggttgca gcacttgtct gggcattagt taacagtggc gacaagaaat gaacgaacaa 44580 acaaaagctg acctgatttt ctacactgaa ctgtatgttg atgcagggta cgactatgaa 44640 gaagctgaac gcatggcgaa agatttgctt cgtgtgattg gtgtgatttt tgatgaggat 44700 aaggtgatat gaaaaattat gaagacatga gtgattcaca aatagcgcaa aaggttttct 44760 tttttgtgag tggtaatctt tgccctaacg gagggttagc tcatatcagt tcagatggct 44820 ttttcttttt tgatgaaaag aacattaaga gaaagtttga cccatgcaac aacccatatg 44880 atgcgtggcc tattattgtt gaaaaccata tcgcagtcgt accatatcaa tacaccatcc 44940 cacaggcttg gcccacggca tttggcgcgg cttcaaagtt caccactgaa gacggaaacc 45000 cactccgcgc tgccatgatt gtctttctga aaatgaatga gggtaaatta tgagtcagtg 45060 gattaagtgt agtgagcgga tgccggaaga aggcaaaatg gttctcacgg cgtttcgtgg 45120 cgtggttaga acagcaatat gcaaaacagc cgatgggaat ggaagcaaga tatttgttag 45180 tgaattagac cgctgccacg gaattccaga tacccattgg gccaatccac cgcaaccacc 45240 acaagaataa aacaaagccc ctttcggggc tttttctttg tcaggatacg gtgcacgcct 45300 tgctgataat aatttccggg tcagtagatg aatccgtgac tgtgacggta tatacaccag 45360 cggtagggct tgccagtgtc gcgccagact taccaccaac aaccgcgcca tctttgcgcc 45420 atacataagt gtaaggagca actccgcctt caacagcaac agttaacggg ctgccagtgc 45480 tgccagttga ttgcaggtcg gtagtgaatg ccagaggctc aaggctttct acggtaacgc 45540 tgtcagaatc gtaaaccttg aactcaaggc taccagtaac gatgtcgttc gtgccacctt 45600 cataactgat gctggtgatg ttgcaatacg cggtaacgat agtagcacca gtcacctcgc 45660 gcacccacaa ggaaggctgg cgacgcgctt tcagttcagt ggcgtaaatc tcaaccaggc 45720 gatggaagcc aaattcatcg ctcgggtcat tcttgcggat ttcaacctct gcgctgatgg 45780 tcatatcaga gctggtaacg agagtggaaa caaatccgcc agcggtatcc gcttccgacg 45840 tagtggtctg cggcgagtag tcaacacctt tgctggtggt tgaacctaaa tacttccagt 45900 cttctgcatc aggaactgcg tcaccgcacc cctcagcaag gaacagtcgg gtcatgcgac 45960 cgaccagaac gcctttatca tttgcacaaa tagccatttc gatctccgaa ttgtgttagc 46020 tgctaacgtg gtgattatat cacaggtgtt gacagtgatt attttgtggt gtagattgta 46080 tttcagatgg ttttcgtgag cgactttgcg gactttttag aaactgacca caaagataaa 46140 tgcaaacgat gatgttgttc tgatggcggc gtaatagcct gtaagtcagc aaggtattcc 46200 gattccttgt aagcaaattc ggcgcactgc gtccctgagg tgtgattaat aagtcaggga 46260 acacaacagg aaagagcatc tcgccaagaa gttgatgcga aagcaatcta agaggtgctc 46320 tttccgttgt gaccagcaag accatacaac acgcgcgata atctcaactg tagcatgtgt 46380 tgcgtggctg ggaatgggtt gacatttaag agtgagatgg tgcgccactc cacaacactt 46440 aatatccagc attatcgcaa tcatatgtag gggtatgtat gggttacggg gctggatatt 46500 aagaaagcac gctggcaatg cttaaaccag cacttatgga cgcgtagctt aattggttaa 46560 agcaaccgac tcataatcgg atgattgaag gttcaaatcc gtccgtgtcc accaaattaa 46620 acaccattag ctcaatggaa agagcagtag ccttctaagc tattggttgc aggttcgaat 46680 cctgcatggt gtgccatcta aactaaaaaa ccacaaatca atccctaagc aattcgcagt 46740 aaaaatttca catagaaatc aagcaatata aaggtaatct catgaattta aattcattat 46800 tcacgtatat aaatggtgaa ctgtactggt ctgcaccagc cgggaataac agaattaagg 46860 ccatgacaaa agctggaaca gttgatgata atggatacat tagggttaag attggtaagt 46920 ctaagcattt agcgcaccgc atcatatggg aaatgcataa cggagcaata cctgacggaa 46980 tggaaattga ccgcataaac cacgacaaga ttgataacag gattgagaat ttaagaatcg 47040 ttagcaggtt aataaatatg caaaataaga gtaaatacaa aaacaattca tcaggagtgt 47100 gtggcgtaag ttggcacaag gttaagtgtt tatgggtgtc gtatatccaa aaaaacaaga 47160 gcagggtcat gcttggttat tttgatgatt tcttcgaggc tgtatgtgcc agaaagtctg 47220 ctgagataag cctcgaattt catagcaatc acggcaaata attacccgta aactaccctt 47280 aataacaatt cgtgaacagg cctcttctct tctgttaaca tcatatcgcc aagcggagat 47340 tgcatctgta tgtagttcag gcagctatca atcgggtttt cttttatgta ttcaattat 47399

Claims (6)

병원성 살모넬라 엔테리티디스균(Salmonella Entritidis)을 특이적으로 사멸시킬 수 있는 능력을 갖는 박테리오파지 KFS-SE2(KCTC 13464BP).Bacteriophage KFS-SE2 (KCTC 13464BP) having the ability to kill pathogenic Salmonella Entebbe utility discharge bacteria (Salmonella Entritidis) specifically. 제1항의 박테리오파지 KFS-SE2(KCTC 13464BP)를 유효성분으로 포함하는 살모넬라 엔테리티디스균의 감염 예방용 조성물.Claim 1 bacteriophage KFS-SE2 (KCTC 13464BP) containing as an active ingredient Salmonella enteritidis infection composition for preventing infection. 제1항의 박테리오파지 KFS-SE2(KCTC 13464BP)를 유효성분으로 포함하는 항생제.An antibiotic comprising the bacteriophage of claim 1 KFS-SE2 (KCTC 13464BP) as an active ingredient. 제1항의 박테리오파지 KFS-SE2(KCTC 13464BP)를 유효성분으로 포함하는 소독제.Disinfectant comprising the bacteriophage of claim 1 KFS-SE2 (KCTC 13464BP) as an active ingredient. 제1항의 박테리오파지 KFS-SE2(KCTC 13464BP)를 유효성분으로 포함하는 사료첨가제.A feed additive comprising the bacteriophage of claim 1 KFS-SE2 (KCTC 13464BP) as an active ingredient. 제1항의 박테리오파지 KFS-SE2(KCTC 13464BP)를 유효성분으로 포함하는 세척제.A cleaning agent comprising the bacteriophage of claim 1 KFS-SE2 (KCTC 13464BP) as an active ingredient.
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Salmonella virus VSt472, complete genome, GenBank: MH424446.1, 2018.09.01.

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