KR20240066489A - Novel bacteriophage LBC1 and uses thereof - Google Patents
Novel bacteriophage LBC1 and uses thereof Download PDFInfo
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- KR20240066489A KR20240066489A KR1020220141713A KR20220141713A KR20240066489A KR 20240066489 A KR20240066489 A KR 20240066489A KR 1020220141713 A KR1020220141713 A KR 1020220141713A KR 20220141713 A KR20220141713 A KR 20220141713A KR 20240066489 A KR20240066489 A KR 20240066489A
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- lbc1
- bacteriophage
- bacillus
- hypothetical protein
- salmonella
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- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
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- C12N2795/00—Bacteriophages
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- C12N2795/00031—Uses of virus other than therapeutic or vaccine, e.g. disinfectant
Abstract
본 발명은 바실러스균, 대장균 또는 살모넬라균에 사멸능을 갖는 박테리오파지, 상기 박테리오파지를 유효성분으로 포함하는 항생제; 소독제; 세척제; 식품 첨가제 조성물; 식품 조성물; 사료 첨가제 조성물; 사료 조성물; 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환 예방 또는 치료용 약학적 조성물; 박테리오파지를 대상에 처리하는 단계를 포함하는 세균 살균 방법에 관한 것이다.The present invention provides a bacteriophage having the ability to kill Bacillus, Escherichia coli or Salmonella, an antibiotic comprising the bacteriophage as an active ingredient; disinfectant; cleaning solution; food additive composition; food composition; feed additive composition; feed composition; Pharmaceutical compositions for preventing or treating infectious diseases caused by Bacillus, Escherichia coli, or Salmonella; It relates to a method of bacterial sterilization including the step of treating a target with bacteriophage.
Description
본 발명은 신규한 박테리오파지 LBC1에 관한 것으로, 구체적으로 상기 박테리오파지 LBC1 및 이의 용도에 관한 것이다.The present invention relates to a novel bacteriophage LBC1, and specifically to the bacteriophage LBC1 and its use.
박테리오파지(bacteriophage)는 특정 세균에만 감염하여 세균의 성장을 통제하는 세균특이적 바이러스로 세균 숙주 없이는 자가 증식이 불가능하며 보통 파지라고 부르기도 한다. 박테리오파지는 단일 혹은 이중 사슬의 DNA 또는 RNA가 유전물질로써 핵산을 구성하고 있으며, 이 핵산을 단백질 외피가 싸고 있는 단순한 구조로 20면체의 머리에 꼬리가 있는 형태, 20면체 머리에 꼬리가 없는 형태, 그리고 필라멘트형의 3가지 기본형 구조로 나뉜다. 가장 흔한 형태인 20면체의 머리에 꼬리가 있는 형태의 박테리오파지는 꼬리 특성에 따라 수축성 꼬리를 가지는 마이오비리대(Myoviridae), 길고 수축성이 없는 꼬리의 시포비리대(Siphoviridae) 그리고 짧은 꼬리의 포도비리대(Podoviridae) 로 세분화될 수 있으며, 20면체의 머리에 꼬리가 없는 박테리오파지는 머리의 형태, 머리의 구성성분 및 외피의 유무에 따라 세분화된다.Bacteriophage is a bacteria-specific virus that infects only specific bacteria and controls the growth of bacteria. It cannot self-proliferate without a bacterial host and is often called a phage. Bacteriophage is a simple structure in which single or double strands of DNA or RNA constitute nucleic acid as genetic material, and this nucleic acid is wrapped in a protein envelope. It has an icosahedral head with a tail, an icosahedral head with no tail, etc. It is divided into three basic filament-type structures. The most common type of icosahedral head-tailed bacteriophage is classified into Myoviridae with a contractile tail, Siphoviridae with a long, non-contractile tail, and Podoviridae with a short tail. (Podoviridae), bacteriophages with an icosahedral head and no tail are subdivided according to the shape of the head, the components of the head, and the presence or absence of an envelope.
세균을 감염시킬때 박테리오파지는 세균의 표면에 달라붙어 자신의 유전물질을 세포 내로 주입한 후 용균성 (lytic) 또는 용원성(lysogenic)을 띠게 된다. 용균성인 경우 박테리오파지가 세포 기구들을 이용하여 자신의 구조물들을 만든 후 새로운 박테리오파지 입자들을 방출시킴으로써 세포를 파괴하거나 용해한다. 용원성인 경우 자신의 핵산을 세균 숙주세포의 염색체에 편입시켜 세균을 파괴하지 않고 세포와 함께 복제되지만 일정 조건이 되면 용균성으로 전환된다.When infecting a bacterium, the bacteriophage attaches to the surface of the bacterium, injects its genetic material into the cell, and then becomes lytic or lysogenic. In the lytic case, the bacteriophage uses cellular machinery to create its own structures and then destroys or lyses the cell by releasing new bacteriophage particles. In the case of lysogeny, the nucleic acid is incorporated into the chromosome of the bacterial host cell and replicates with the cell without destroying the bacterium, but under certain conditions, it converts to lytic.
박테리오파지의 발견 이후 이를 감염질병 치료제로 이용하기 위한 연구가 진행되었지만 광범위한 숙주범위(broad target spectrum)를 갖는 항생제의 특성에 비해 숙주특이성(specific target spectrum)을 갖는 박테리오파지가 경쟁에서 밀려나 관심을 받지 못했다. 항생제 혹은 항균제는 세균 감염에 의한 감염성 질환의 치료에 널리 사용되고 있지만 항생제의 오남용으로 항생제 내성균의 문제가 심각해지고, 식품내의 항생제 잔류가 인체에 미칠 영향에 대한 우려가 높아짐에 따라 항생제에 비하여 숙주 특이성이 높은 박테리오파지에 대한 관심이 높아지고 있다.After the discovery of bacteriophages, research was conducted to use them as a treatment for infectious diseases, but compared to the characteristics of antibiotics with a broad target spectrum, bacteriophages with a specific target spectrum were outcompeted and did not receive attention. Antibiotics or antibacterial agents are widely used in the treatment of infectious diseases caused by bacterial infections, but the problem of antibiotic-resistant bacteria is becoming more serious due to misuse of antibiotics, and as concerns about the impact of antibiotic residues in food on the human body are increasing, host specificity is lower than that of antibiotics. There is increasing interest in highly bacteriophages.
한편, 바실러스(Bacillus)는 그람 양성의 간균으로 아포를 형성하고 편모를 갖는 세균이다. 바실러스 세레우스(Bacillus cereus)는 산소 조건에서 잘 증식하는 호기성 세균으로 7~49℃에서 발육하며, 최적온도는 28~35℃이다. 다른 바실러스 속과 구별되는 특징으로는 β-용혈 현상을 가지고 있고, 레시틴 분해효소(lecithinase)를 생성하여 난황반응(egg-yolk reaction)에서 집락 주변이 유백색을 띄는 양상을 나타낸다. 바실러스 세레우스는 토양이나 물 등 자연계에 널리 분포하고, 열에 강한 포자를 형성하여 식품 등을 오염시킨다. 특히 쌀, 유제품, 육류, 향신료 등의 식품 원료나, 이를 가공한 식품에서 검출이 빈번하다. 1955년, 노르웨이에서 식중독 원인균으로 처음 보고가 되었으며 이후 영국 등 유럽에서의 발병사례가 많아 주목을 받아왔다. 최근 우리나라에서도 각종 식품에서 검출되어 주요 식중독 원인 균주로 규제 대상이 되고 있다. 바실러스 세레우스에 의한 식중독은 두 가지로 나뉠 수 있는데, 장 독소(enterotoxin)를 원인 독소로 하는 설사형과 구토 독소(emetic toxin)를 원인 독소로 하는 구토형으로 두 가지 형태가 있다. 설사형인 경우 바실러스 세레우스가 인체 장관 내에서 증식하면서 장독소를 생산하여 발생되며, 독소 활성은 내열성이 높아서 120℃, 20분 가열하여도 파괴되지 않는다. 구토형인 경우 오염된 식품 섭취 후 균이 증식하면서 구토형 독소인 구토 독소에 의해 발생하며 구토, 오심, 복통을 유발한다. 독소는 126℃, 90분간 가열하여도 파괴되지 않으며 산, 알칼리 및 단백질 가수분해 효소에도 저항성을 갖는다. 바실러스 세레우스에 의한 식중독은 대부분의 경우 식품 중에 존재하는 바실러스 세레우스 생장세포나 포자가 105~108/g 존재할 경우 발생한다. 바실러스 세레우스의 포자는 강한 접착성을 지녔으며 어느 표면이든 잘 부착하여 세척과 소독에 어려움이 있다. 그리고 물체 표면에 부착 후 바이오필름을 형성하여 농업, 축산업, 식품산업 등에서 제어하기 어려운 문제가 되고 있다. 바실러스 세레우스의 포자가 강한 접착성을 지니는 것은 포자가 상대적으로 높은 소수성을 지녔고 포자의 표면이 낮은 전하를 띄고 긴 부속사(appendage)가 포자를 싸고 있는 형태 때문이다. 이렇듯 바실러스 세레우스는 자연에 널리 분포되어 있고 그 특성으로 인하여 식품 중 오염을 방지하기는 어려우므로 가열, 염화나트륨, 유기산, 에탄올, 전자선 조사(electron beam irradiation) 등의 물리적, 화학적 제어법을 이용하여 사멸시키거나 증식을 억제한다. 하지만, 소비자들은 식품 내에 상기 물질의 함유 및 최소한의 가공 처리를 원하기 때문에 인체 유익한 미생물에는 무해하며 유해 미생물만을 선택적으로 사멸시킬 수 있는 새로운 방법의 식품 보존 및 살균제가 요구되는 상황이다. Meanwhile, Bacillus is a Gram-positive bacillus that forms spores and has flagella. Bacillus cereus is an aerobic bacterium that proliferates well under oxygen conditions and grows at 7 to 49°C, with an optimal temperature of 28 to 35°C. Characteristics that distinguish it from other Bacillus genera include β-hemolysis and the production of lecithinase, which gives the colony a milky white appearance during the egg-yolk reaction. Bacillus cereus is widely distributed in the natural world, including soil and water, and contaminates food by forming heat-resistant spores. In particular, detection is frequent in food raw materials such as rice, dairy products, meat, and spices, or in foods processed from them. In 1955, it was first reported as the causative agent of food poisoning in Norway, and has since received attention due to the many cases of the disease in Europe, including the UK. Recently, it has been detected in various foods in Korea and is subject to regulation as a major cause of food poisoning. Food poisoning caused by Bacillus cereus can be divided into two types: a diarrheal type caused by enterotoxin and an emetic type caused by an emetic toxin. The diarrheal form is caused by Bacillus cereus proliferating in the human intestinal tract and producing enterotoxins. The toxin activity is highly heat-resistant and is not destroyed even when heated at 120°C for 20 minutes. In the case of the vomiting type, it is caused by vomiting toxin, a vomiting type toxin, when bacteria proliferate after eating contaminated food, causing vomiting, nausea, and abdominal pain. The toxin is not destroyed even when heated at 126°C for 90 minutes and is resistant to acids, alkalis, and proteolytic enzymes. In most cases, food poisoning caused by Bacillus cereus occurs when there are 10 5 to 10 8 /g of Bacillus cereus growth cells or spores present in food. Bacillus cereus spores have strong adhesive properties and adhere well to any surface, making cleaning and disinfection difficult. Additionally, it forms a biofilm after attaching to the surface of an object, making it a difficult problem to control in agriculture, livestock, and food industries. The reason why the spores of Bacillus cereus have strong adhesive properties is because the spores have relatively high hydrophobicity, the surface of the spores has a low charge, and the long appendages surround the spores. As such, Bacillus cereus is widely distributed in nature, and due to its characteristics, it is difficult to prevent contamination in food, so it is killed using physical and chemical control methods such as heating, sodium chloride, organic acids, ethanol, and electron beam irradiation. or inhibit proliferation. However, because consumers want the inclusion of the above-mentioned substances in food and minimal processing, there is a need for a new method of food preservation and disinfectant that is harmless to beneficial microorganisms and can selectively kill only harmful microorganisms.
이러한 배경하에서, 본 발명자들은 바실러스 세레우스 뿐만 아니라 대장균 및 살모넬라균에도 용균 활성을 갖는 신규 박테리오파지를 개발함으로써 이를 포함하는 항균 조성물을 이용하여 바실러스 세레우스, 대장균 또는 살모넬라균으로 인한 감염성 질병 예방 또는 치료용 약학적 조성물, 항생제, 소독제 등에 사용할 수 있음을 확인하여 본 발명을 완성하였다.Under this background, the present inventors developed a new bacteriophage that has lytic activity not only on Bacillus cereus but also on E. coli and Salmonella, and used an antibacterial composition containing it to prevent or treat infectious diseases caused by Bacillus cereus, E. coli, or Salmonella. The present invention was completed by confirming that it can be used in pharmaceutical compositions, antibiotics, disinfectants, etc.
본 발명의 목적은 바실러스균, 대장균 또는 살모넬라균에 대한 특이적 사멸능을 갖는 박테리오파지를 제공하는 것이다.The purpose of the present invention is to provide a bacteriophage having a specific killing ability against Bacillus, E. coli or Salmonella.
본 발명의 다른 목적은 박테리오파지를 유효성분으로 포함하는 항생제를 제공하는 것이다.Another object of the present invention is to provide an antibiotic containing bacteriophage as an active ingredient.
본 발명의 다른 목적은 박테리오파지를 유효성분으로 포함하는 소독제를 제공하는 것이다.Another object of the present invention is to provide a disinfectant containing bacteriophage as an active ingredient.
본 발명의 다른 목적은 박테리오파지를 유효성분으로 포함하는 세척제를 제공하는 것이다.Another object of the present invention is to provide a detergent containing bacteriophage as an active ingredient.
본 발명의 다른 목적은 박테리오파지를 유효성분으로 포함하는 식품 첨가제 조성물; 식품 조성물을 제공하는 것이다.Another object of the present invention is a food additive composition containing bacteriophage as an active ingredient; To provide a food composition.
본 발명의 다른 목적은 박테리오파지를 유효성분으로 포함하는 사료 첨가제 조성물; 사료 조성물을 제공하는 것이다.Another object of the present invention is a feed additive composition containing bacteriophage as an active ingredient; To provide a feed composition.
본 발명의 다른 목적은 박테리오파지를 유효성분으로 포함하는 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환 예방 또는 치료용 약학적 조성물을 제공하는 것이다.Another object of the present invention is to provide a pharmaceutical composition for preventing or treating infectious diseases caused by Bacillus, Escherichia coli, or Salmonella, containing bacteriophage as an active ingredient.
본 발명의 다른 목적은 박테리오파지를 대상에 처리하는 단계를 포함하는, 세균 살균 방법을 제공하는 것이다.Another object of the present invention is to provide a method for sterilizing bacteria, including the step of treating a target with bacteriophage.
이를 구체적으로 설명하면 다음과 같다. 한편, 본 출원에서 개시된 각각의 설명 및 실시형태는 각각의 다른 설명 및 실시 형태에도 적용될 수 있다. 즉, 본 출원에서 개시된 다양한 요소들의 모든 조합이 본 출원의 범주에 속한다. 또한, 하기 기술된 구체적인 서술에 의하여 본 출원의 범주가 제한된다고 볼 수 없다.This is explained in detail as follows. Meanwhile, each description and embodiment disclosed in the present application may also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in this application fall within the scope of this application. Additionally, the scope of the present application cannot be considered limited by the specific description described below.
본 발명자들은 아래의 실시예 및 실험예에서 확인되는 바와 같이, 본 발명의 신규 박테리오파지 LBC1(수탁번호 KCTC 15078BP)을 자연계에서 분리하였으며, 신규 박테리오파지 LBC1의 형태적, 생화학적 및 유전적 특성을 확인한 결과, 바실러스균, 대장균 또는 살모넬라균에 대한 생육 억제 또는 사멸능을 확인함으로써 본 발명을 완성하였다.As confirmed in the examples and experimental examples below, the present inventors isolated the new bacteriophage LBC1 of the present invention (accession number KCTC 15078BP) from the natural world, and confirmed the morphological, biochemical and genetic characteristics of the new bacteriophage LBC1. , the present invention was completed by confirming the growth inhibition or killing ability for Bacillus, E. coli, or Salmonella bacteria.
상기 목적을 달성하기 위한 일 양태로서, 본 발명은 바실러스균, 대장균 또는 살모넬라균에 대한 특이적 사멸능을 갖는 박테리오파지를 제공한다.As an aspect for achieving the above object, the present invention provides a bacteriophage having a specific killing ability against Bacillus, Escherichia coli, or Salmonella.
본 명세서에서 사용되는 용어 "박테리오파지(bacteriophage)"는 특정 세균에 감염하여 당해 세균의 성장을 억제하고 저해하는 세균 특이적 바이러스로, 단일 혹은 이중 사슬의 DNA 또는 RNA를 유전 물질로 포함하는 바이러스를 의미한다.As used herein, the term "bacteriophage" is a bacteria-specific virus that infects a specific bacterium and inhibits and inhibits the growth of that bacterium, a virus containing single or double stranded DNA or RNA as genetic material. means.
본 명세서에서 사용되는 용어 "바실러스균"은 간균속(바실러스속)에 속하는 그람 양성균으로 바실러스 세레우스(Bacillus cereus), 바실러스 마이코이데스(Bacillus mycoides), 바실러스 파라마이코이데스(Bacillus paramycoides) 또는 바실러스 투린지엔시스(Bacillus thuringiensis) 일 수 있으나 이에 한정되는 것은 아니다.The term "Bacillus" used in this specification refers to Gram-positive bacteria belonging to the genus Bacillus, including Bacillus cereus , Bacillus mycoides , and Bacillus paramycoides . Or it may be Bacillus thuringiensis , but it is not limited thereto.
본 명세서에서 사용되는 용어 "대장균"은 간균에 속하는 장내세균으로 그람 음성균에 속하는 균을 의미한다. 대부분의 대장균은 상재균으로 병원균이 아니나 E. coli O157:H7이나 장내독소형 대장균 (ETEC, enterotoxigenic E. coli) 등은 병원성 대장균으로서 사람에게서 식중독을 유발하거나, 소, 돼지, 염소 등의 여러 동물들에서 설사를 일으키는 것으로 알려져 있다.The term "E. coli" used in this specification refers to enteric bacteria belonging to the bacillus group and belonging to Gram-negative bacteria. Most E. coli are common bacteria and are not pathogens, but E. coli O157:H7 and enterotoxigenic E. coli (ETEC) are pathogenic E. coli and cause food poisoning in humans or various animals such as cattle, pigs, and goats. It is known to cause diarrhea in the fields.
본 명세서에서 사용되는 용어 "병원성 대장균"은 사람이나 동물의 대장에 서식하는 병독인자를 지닌 대장균으로, 장병원성 대장균(Enteropathogenic E. coli, EPEC), 장출혈성 대장균(Enterohemorrhagic E. coli, EHEC), 장독소형 대장균(Enterotoxigenic E. coli, ETEC), 장관응집성 대장균(Enteroaggregative E. coli, EAEC), 장침입성대장균(Enteroinvasive E. coli, EIEC) 또는 장관확산부착성 대장균(Diffusely adherent E. coli, DAEC) 일 수 있으나 이에 한정되는 것은 아니다.The term "pathogenic E. coli" used in this specification refers to E. coli with virulence factors that live in the large intestine of humans or animals, including Enteropathogenic E. coli (EPEC) and Enterohemorrhagic E. coli (EHEC). ), Enterotoxigenic E. coli (ETEC), Enteroaggregative E. coli (EAEC), Enteroinvasive E. coli (EIEC), or Diffusely adherent E. coli DAEC), but is not limited to this.
본 명세서에서 사용되는 용어 “살모넬라균”은 장내세균과에 속하는 그람음성의 통성혐기성 세균으로 살모넬라 엔테리티디스(S. Enteritidis), 살모넬라 티피뮤리움(S. Typhimurium), 살모넬라 타이피(S. Typhi) 또는 살모넬라 파라티피(S. Paratyphi)일 수 있으나 이에 한정되지 않는다.The term “Salmonella” used in this specification refers to Gram-negative facultative anaerobic bacteria belonging to the Enterobacteriaceae family, including Salmonella Enteritidis, Salmonella Typhimurium, and S. Typhi. ) or Salmonella Paratyphi ( S. Paratyphi), but is not limited thereto.
상기 박테리오파지는 서열번호 1로 표시되는 염기서열을 전체 유전자의 전체 또는 일부로서 포함할 수 있다. 또한, 본 발명의 박테리오파지는 서열번호 1로 표시되는 염기서열, 및 상기 염기서열의 기능적 동등물로 이루어질 수 있다. 상기 기능적 동등물이란 염기서열의 변형, 치환의 결과, 상기 서열번호 1로 표시되는 염기서열과 적어도 70%이상, 구체적으로 80% 이상, 더욱 구체적으로 90% 이상, 더더욱 구체적으로는 95% 이상의 서열 상동성을 갖는 것으로, 서열번호 1로 표시되는 염기서열과 실질적으로 동질의 생리활성을 나타내는 서열을 의미한다.The bacteriophage may include the base sequence represented by SEQ ID NO: 1 as all or part of the entire gene. In addition, the bacteriophage of the present invention may consist of the base sequence represented by SEQ ID NO: 1 and a functional equivalent of the base sequence. The functional equivalent refers to a sequence that is at least 70% or more, specifically 80% or more, more specifically 90% or more, and even more specifically 95% or more of the base sequence represented by SEQ ID NO. 1 as a result of modification or substitution of the base sequence. Having homology, it means a sequence that exhibits substantially the same physiological activity as the base sequence represented by SEQ ID NO: 1.
상기 목적을 달성하기 위한 또 다른 양태로서, 본 발명은 박테리오파지를 유효성분으로 포함하는 항생제를 제공한다.As another aspect for achieving the above object, the present invention provides an antibiotic containing bacteriophage as an active ingredient.
본 명세서 사용되는 용어, "항생제"는 균을 죽이거나 균의 성장을 억제할 수 있는 제제를 의미하며, 방부제, 살균제 및 항균제를 총칭하는 것일 수 있다.As used herein, the term "antibiotic" refers to an agent that can kill bacteria or inhibit the growth of bacteria, and may be a general term for preservatives, disinfectants, and antibacterial agents.
본 명세서에서 사용되는 용어 "유효성분"이란 단독으로 목적하는 활성을 나타내거나 또는 그 자체는 활성이 없는 담체와 함께 활성을 나타낼 수 있는 성분을 의미한다.As used herein, the term "active ingredient" refers to an ingredient that exhibits the desired activity alone or can exhibit activity together with a carrier that is not active on its own.
상기 박테리오파지를 유효성분으로 포함하는 항생제는 종래 항생제에 비하여 익균은 죽이지 않고 특정 병원균만을 사멸시킬 수 있으며, 약물 내성을 유도하지 않아 종래의 항생제에 비하여 제품 수명이 연장되는 효과를 나타낼 수 있다.Compared to conventional antibiotics, antibiotics containing the bacteriophage as an active ingredient can kill only specific pathogens without killing beneficial bacteria, and do not induce drug resistance, which can have the effect of extending product lifespan compared to conventional antibiotics.
상기 항생제는 당업계에서 통상적으로 사용되는 제조방법에 의해 제조될 수 있다.The antibiotic can be manufactured by a manufacturing method commonly used in the art.
상기 항생제는 항생제의 품질 저하를 감소시키는데 충분한 유효량의 첨가제를 포함하는 것일 수 있고, 상기 첨가제는 보존제, 안정화제, 부형제 또는 동결보호제 등일 수 있다. 상기 항생제는 상기 첨가제를 포함함으로써, 자연 상태에 존재하는 박테리오파지와 다르게, 항생제 내에서 박테리오파지가 보다 오랜 기간 동안 생존하거나 활성이 유지되는 것일 수 있다. 상기 보존제, 안정화제, 부형제 또는 동결보호제는 항생제의 품질 저하를 감소시킬 수 있는 것이면 당업계에서 통상적으로 사용되는 것들이 제한 없이 사용될 수 있다.The antibiotic may contain an effective amount of an additive sufficient to reduce quality degradation of the antibiotic, and the additive may be a preservative, stabilizer, excipient, or cryoprotectant. By including the additive, the antibiotic may allow the bacteriophage to survive or maintain activity for a longer period of time within the antibiotic, unlike bacteriophages that exist in nature. The preservatives, stabilizers, excipients, or cryoprotectants may be those commonly used in the art without limitation as long as they can reduce the quality degradation of antibiotics.
상기 목적을 달성하기 위한 또 다른 양태로서, 본 발명은 박테리오파지를 유효성분으로 포함하는 소독제를 제공한다. 또 다른 양상은 상기 박테리오파지를 유효성분으로 포함하는 세척제를 제공한다. 상기 용어 박테리오파지, 유효성분 등은 전술한 바와 같다.As another aspect for achieving the above object, the present invention provides a disinfectant containing bacteriophage as an active ingredient. Another aspect provides a detergent containing the bacteriophage as an active ingredient. The terms bacteriophage, active ingredient, etc. are as described above.
상기 소독제 또는 세척제의 제형은 특별히 제한되지 아니하며 당업계에서 통상적으로 알려진 제형으로 제조되어 사용될 수 있다. 상기 소독제 또는 세척제는 당업계에서 통상적으로 사용되는 제조방법에 의해 제조될 수 있다.The formulation of the disinfectant or cleaner is not particularly limited, and formulations commonly known in the art can be prepared and used. The disinfectant or cleaner can be manufactured by a manufacturing method commonly used in the art.
상기 소독제는 바실러스균, 대장균 또는 살모넬라균을 제거하기 위하여 살포될 수 있으며 동물의 활동 영역, 도축장, 폐사 지역, 조리 장소 또는 조리 설비 등에 살포될 수 있으나 이에 한정되는 것은 아니다.The disinfectant may be sprayed to remove Bacillus bacteria, E. coli, or Salmonella bacteria, and may be sprayed on animal activity areas, slaughterhouses, death areas, cooking areas, or cooking equipment, but is not limited thereto.
상기 세척제는 바실러스균, 대장균 또는 살모넬라균에 노출되었거나 노출될 가능성이 있는 동물의 피부 표면 또는 신체 각 부위 등을 세척하는 용도로 사용될 수 있으나 이에 한정되는 것은 아니다.The detergent may be used to clean the skin surface or body parts of animals that have been or may be exposed to Bacillus, E. coli, or Salmonella, but is not limited thereto.
상기 소독제 또는 세척제는 이들의 품질 저하를 감소시키는데 충분한 유효량의 첨가제를 포함하는 것일 수 있고, 상기 첨가제는 보존제, 안정화제, 부형제, 또는 동결보호제 등일 수 있다. 상기 소독제 또는 세척제는 상기 첨가제를 포함함으로써, 자연상태에 존재하는 박테리오파지와 다르게, 소독제 또는 세척제 내에서 박테리오 파지가 보다 오랜 기간 동안 생존하거나 활성이 유지되는 것일 수 있다. 상기 보존제, 안정화제, 부형제 또는 동결보호제는 소독제 또는 세척제의 품질 저하를 감소시킬 수 있는 것이면, 당업계에서 통상적으로 사용되는 것들이 제한 없이 사용될 수 있다.The disinfectant or cleaner may contain an effective amount of an additive sufficient to reduce quality degradation, and the additive may be a preservative, stabilizer, excipient, or cryoprotectant. By containing the additive, the disinfectant or cleaner may allow the bacteriophage to survive or remain active for a longer period of time in the disinfectant or cleaner, unlike bacteriophages that exist in nature. The preservatives, stabilizers, excipients or cryoprotectants can be those commonly used in the art without limitation, as long as they can reduce the quality deterioration of the disinfectant or cleaning agent.
상기 목적을 달성하기 위한 또 다른 양태로서, 본 발명은 박테리오파지를 유효성분으로 포함하는 식품 첨가제 조성물 또는 식품 조성물을 제공한다. As another aspect for achieving the above object, the present invention provides a food additive composition or food composition containing bacteriophage as an active ingredient.
본 발명의 식품 조성물에 포함되는 박테리오파지는 상술한 바와 같이, 바실러스균, 대장균 또는 살모넬라균을 특이적으로 사멸시키므로, 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환에 개선 효과를 나타내며, 이러한 효과를 가지는 한, 다양한 함량으로 포함할 수 있다.As described above, the bacteriophage included in the food composition of the present invention specifically kills Bacillus, E. coli, or Salmonella, and thus has an improving effect on infectious diseases caused by Bacillus, E. coli, or Salmonella, and has this effect. As long as it can be included in various amounts.
본 명세서에서 사용되는 용어 "개선"은 바실러스균, 대장균 또는 살모넬라균에 의해 유발된 질환의 경감을 의미한다.The term "improvement" used in this specification refers to the reduction of diseases caused by Bacillus, E. coli, or Salmonella.
본 명세서에서 사용되는 용어 "바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환"은 바실러스균 감염증, 식중독, 대장균 감염증, 출혈성 대장염, 요독증후군, 혈소판 감소성 자반증, 살모넬라균 감염증, 또는 장티푸스 일 수 있으나 이에 한정되는 것은 아니다.As used herein, the term "infectious disease caused by Bacillus bacteria, E. coli or Salmonella bacteria" may mean Bacillus infection, food poisoning, E. coli infection, hemorrhagic colitis, uremic syndrome, thrombocytopenic purpura, salmonella infection, or typhoid fever. However, it is not limited to this.
본 발명의 식품 조성물은 박테리오파지 이외에, 복용이나 섭취의 편리성을 증진시키기 위하여, 당업계에서 이미 안전성이 검증되고 해당 활성을 갖는 것으로 공지된 임의의 화합물이나 천연 추출물을 추가로 포함할 수 있다.In addition to the bacteriophage, the food composition of the present invention may further include any compound or natural extract whose safety has already been verified in the art and known to have the corresponding activity in order to improve the convenience of taking or ingesting.
이러한 화합물 또는 추출물에는 각국 약전(한국에서는 '대한민국약전'), 각국 건강기능식품공전(한국에서는 식약처 고시인 '건강기능식품 기준 및 규격') 등의 공정서에 실려 있는 화합물 또는 추출물, 의약품의 제조·판매를 규율하는 각국의 법률(한국에서는 '약사법')에 따라 품목 허가를 받은 화합물 또는 추출물, 건강기능식품의 제조·판매를 규율하는 각국 법률(한국에서는 '건강기능식품에 관한 법률')에 따라 기능성이 인정된 화합물 또는 추출물이 포함될 수 있다.These compounds or extracts include compounds, extracts, and medicinal products listed in compendiums such as the Pharmacopoeia of each country ('Korean Pharmacopoeia' in Korea) and the Code of Health Functional Foods of each country ('Standards and Specifications for Health Functional Foods' notified by the Ministry of Food and Drug Safety in Korea). The laws of each country governing the manufacture and sale of compounds, extracts, and health functional foods that have received product approval in accordance with the laws of each country that govern the manufacture and sale ('Pharmaceutical Affairs Act' in Korea) (the 'Act on Health Functional Foods' in Korea) Accordingly, compounds or extracts with recognized functionality may be included.
본 발명의 용어 "식품"은 육류, 소시지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료, 비타민 복합제, 영양 보조제(nutritional supplement), 기능성 식품, 식품 첨가제(food additive), 건강 기능 식품 및 건강 식품 등이 있으며, 통상적인 의미의 식품을 모두 포함한다. The term "food" of the present invention refers to dairy products including meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, and ice cream, various soups, beverages, tea, drinks, and alcohol. It includes beverages, vitamin complexes, nutritional supplements, functional foods, food additives, health functional foods, and health foods, and includes all foods in the conventional sense.
본 발명의 용어 "건강 기능 식품"이란, 특정보건용 식품(food for special health use, FoSHU)와 동일한 용어로, 영양 공급 외에도 생체조절기능이 효율적으로 나타나도록 가공된 의학, 의료효과가 높은 식품을 의미한다. 여기서 "기능(성)"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 식품은 당업계에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조시에는 당업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 상기 식품의 제형 또한 식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 식품 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나며, 본 발명의 식품은 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환 개선을 위한 보조제로 섭취가 가능하다.The term "health functional food" of the present invention is the same as food for special health use (FoSHU), which refers to medicine processed to efficiently exhibit bioregulatory functions in addition to nutritional supply, with high medical effectiveness. It means food. Here, "function" means controlling nutrients for the structure and function of the human body or obtaining useful effects for health purposes, such as physiological effects. The food of the present invention can be manufactured by methods commonly used in the industry, and can be manufactured by adding raw materials and ingredients commonly added in the industry. Additionally, the food formulation can be manufactured without limitation as long as it is a formulation recognized as a food. The food composition of the present invention can be manufactured in a variety of dosage forms, and unlike general drugs, it has the advantage of being made from food as a raw material and has no side effects that may occur when taking the drug for a long period of time, is excellent in portability, and Food can be consumed as a supplement to improve infectious diseases caused by Bacillus, E. coli, or Salmonella.
구체적으로, 상기 건강 기능 식품은 박테리오파지를 음료, 차류, 향신료, 껌, 과자류 등의 식품소재에 첨가하거나, 환, 정제, 캡슐, 분말, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용이 없는 장점이 있다.Specifically, the health functional foods are foods made by adding bacteriophages to food materials such as beverages, teas, spices, gum, and confectionery, or manufactured into pills, tablets, capsules, powders, suspensions, etc., and consuming them may cause certain health problems. It means bringing about an effect, but unlike regular drugs, it has the advantage of not having any side effects that may occur when taking the drug for a long time since it is made from food.
본 발명의 식품 조성물은, 일상적으로 섭취하는 것이 가능하기 때문에 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환 개선 효과를 기대할 수 있어 매우 유용하다.The food composition of the present invention is very useful because it can be consumed on a daily basis and can be expected to improve infectious diseases caused by Bacillus, Escherichia coli, or Salmonella.
본 발명의 식품 조성물은 어떠한 형태로도 제조될 수 있으며, 예컨대 차, 쥬스, 탄산음료, 이온음료 등의 음료류, 우유, 요구루트 등의 가공 유류(乳類), 껌류, 떡, 한과, 빵, 과자, 면 등의 식품류, 정제, 캡슐, 환, 과립, 액상, 분말, 편상, 페이스트상, 시럽, 겔, 젤리, 바 등의 제제류 등으로 제조될 수 있다. 또한, 본 발명의 식품 조성물은 법률상·기능상의 구분에 있어서 제조·유통 시점의 시행 법규에 부합하는 한 임의의 제품 구분을 띨 수 있다. 예컨대 한국 '건강기능식품에 관한 법률'에 따른 건강기능식품이거나, 한국 '식품위생법'의 식품공전(식약처 고시 '식품의 기준 및 규격')상 각 식품유형에 따른 과자류, 다류, 음료류, 특수용도식품 등일 수 있다.The food composition of the present invention can be manufactured in any form, for example, beverages such as tea, juice, carbonated beverages, and electrolyte drinks, processed oils such as milk and yogurt, gums, rice cakes, Korean snacks, bread, It can be manufactured into foods such as snacks and noodles, and preparations such as tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars, etc. In addition, the food composition of the present invention may have any product classification in terms of legal and functional classification as long as it complies with the enforcement laws and regulations at the time of manufacture and distribution. For example, it is a health functional food according to Korea's 'Act on Health Functional Foods', or confectionery, tea, beverages, and special food according to each food type according to the food code of Korea's 'Food Sanitation Act' (Ministry of Food and Drug Safety Notification 'Food Standards and Specifications'). It may be food for use, etc.
또한, 본 발명의 식품 조성물에는 그 유효성분 이외에 식품첨가물이 포함될 수 있다. 식품첨가물은 일반적으로 식품을 제조, 가공 또는 보존함에 있어 식품에 첨가되어 혼합되거나 침윤되는 물질로서 이해될 수 있는데, 식품과 함께 매일 그리고 장기간 섭취되므로 그 안전성이 보장되어야 한다. 이러한 식품첨가물은 용도면에 있어서는 감미료, 향미증진제, 보존료, 유화제, 향료 등으로 구분된다.Additionally, the food composition of the present invention may contain food additives in addition to the active ingredients. Food additives can generally be understood as substances that are added to, mixed with, or infiltrated into food when manufacturing, processing, or preserving food. Since they are consumed daily and for a long period of time with food, their safety must be guaranteed. In terms of use, these food additives are divided into sweeteners, flavor enhancers, preservatives, emulsifiers, and flavorings.
상기 감미료는 식품에 적당한 단맛을 부여하기 위하여 사용되는 것으로, 천연의 것이거나 합성된 것을 사용할 수 있다. 예를 들어, 네오탐, 락티톨, D-리보오스, 만니톨, D-말티톨, 사카린나트륨 등의 감미료가 사용될 수 있다.The sweetener is used to impart an appropriate sweetness to food, and can be either natural or synthetic. For example, sweeteners such as neotame, lactitol, D-ribose, mannitol, D-maltitol, and sodium saccharin can be used.
상기 향미증진제는 식품의 맛이나 향을 증진시키는 식품 첨가물로, 천연의 것과 합성된 것 모두 사용될 수 있다. 예를 들어, 향미증진제는 5'-구아닐산이나트륨, L-글루탐산, 글리신, 베타인 등이 사용될 수 있다.The flavor enhancer is a food additive that enhances the taste or aroma of food, and both natural and synthetic agents can be used. For example, flavor enhancers may include disodium 5'-guanylate, L-glutamic acid, glycine, betaine, etc.
상기 보존료로서는 메타중아황산나트륨, 무수아황산, 소브산, 안식향산, 자몽종자추출물 등이 사용될 수 있다.As the preservative, sodium metabisulfite, sulfurous anhydride, sorbic acid, benzoic acid, grapefruit seed extract, etc. may be used.
상기 유화제는 물과 기름 등 섞이지 않는 두 가지 또는 그 이상의 상(phases)을 균질하게 섞어주거나 유지시키는 식품첨가물로, 글루콘산나트륨, 글리세린지방산에스테르, 레시틴, 스테아린산마그네슘, 알긴산 등이 사용될 수 있다.The emulsifier is a food additive that homogeneously mixes or maintains two or more immiscible phases such as water and oil, and may include sodium gluconate, glycerin fatty acid ester, lecithin, magnesium stearate, alginic acid, etc.
상기 향료는 식품에 특유한 향을 부여하거나 제조공정 중 손실된 식품 본래의 향을 보강시키는 식품첨가물로, 에틸바닐린, 옥탄산에틸, 초산리나릴, 카프론산알릴, 파라메틸아세토페논 등이 사용될 수 있다.The flavoring agent is a food additive that gives a unique flavor to food or reinforces the original flavor of food lost during the manufacturing process. Ethyl vanillin, ethyl octanoate, linalyl acetate, allyl caproate, paramethylacetophenone, etc. may be used. .
본 발명의 식품 조성물은 전술한 바의 식품첨가물 이외에, 기능성과 영양성을 보충, 보강할 목적으로 당업계에 공지되고 식품첨가물로서 안정성이 보장된 생리활성 물질이나 미네랄류를 포함할 수 있다. 상기 생리활성 물질로는 녹차 등에 포함된 카테킨류, 비타민 B1, 비타민 C, 비타민 E, 비타민 B12 등의 비타민류, 토코페롤, 디벤조일티아민 등을 들 수 있으며, 미네랄류로서는 구연산칼슘 등의 칼슘 제제, 스테아린산마그네슘 등의 마그네슘 제제, 구연산철 등의 철 제제, 염화크롬, 요오드칼륨, 셀레늄, 게르마늄, 바나듐, 아연 등을 들 수 있다.In addition to the food additives described above, the food composition of the present invention may contain bioactive substances or minerals known in the art and whose safety is guaranteed as food additives for the purpose of supplementing and reinforcing functionality and nutrition. The bioactive substances include catechins contained in green tea, vitamins such as vitamin B1, vitamin C, vitamin E, and vitamin B12, tocopherol, and dibenzoylthiamine. Minerals include calcium preparations such as calcium citrate and stearic acid. Magnesium preparations such as magnesium, iron preparations such as iron citrate, chromium chloride, potassium iodide, selenium, germanium, vanadium, zinc, etc. are included.
본 발명의 식품 조성물에는 전술한 바의 식품첨가물이 제품 유형에 따라 그 목적을 달성할 수 있는 적정량으로 포함될 수 있으며, 본 발명의 식품 조성물에 포함될 수 있는 기타의 식품첨가물과 관련하여서는 각국 식품공전이나 식품첨가물 공전을 참조할 수 있다.The food composition of the present invention may contain the above-described food additives in an appropriate amount to achieve the purpose depending on the product type, and with respect to other food additives that may be included in the food composition of the present invention, each country's food code or You can refer to the Food Additives Code.
상기 목적을 달성하기 위한 또 다른 양태로서, 본 발명은 박테리오파지를 유효성분으로 포함하는 사료 첨가제 조성물 또는 사료 조성물을 제공한다. 상기 용어 박테리오파지, 유효성분 등은 전술한 바와 같다.As another aspect for achieving the above object, the present invention provides a feed additive composition or feed composition containing bacteriophage as an active ingredient. The terms bacteriophage, active ingredient, etc. are as described above.
상기 사료 첨가제는 박테리오파지를 포함하는 조성물의 형태로 제조되어 사료에 혼합시키거나, 상기 박테리오파지를 사료 제조시 직접 첨가하는 방식으로 사용하는 것일 수 있다.The feed additive may be prepared in the form of a composition containing bacteriophage and mixed into feed, or may be used by directly adding the bacteriophage during feed production.
상기 사료 첨가제 내에 포함되는 박테리오파지는 액체 상태 또는 건조된 고체 상태일 수 있고, 구체적으로, 건조된 분말 형태일 수 있다. 상기 박테리오파지의 건조 방법은 통풍 건조, 자연 건조, 분무 건조 또는 동결 건조 방법일 수 있으나 이에 제한되지 않는다.The bacteriophage contained in the feed additive may be in a liquid state or a dried solid state, and specifically, may be in the form of a dried powder. The drying method of the bacteriophage may be ventilation drying, natural drying, spray drying, or freeze drying, but is not limited thereto.
상기 박테리오파지를 유효성분으로 포함하는 사료 첨가제는 필요에 따라 기타 첨가제를 추가로 포함할 수 있다. 상기 사용 가능한 첨가제의 비제한적인 예로는, 사료의 품질 저하를 방지하기 위하여 첨가하는 결합제, 유화제, 보존제; 사료의 효용 증대를 위하여 첨가하는 아미노산제, 비타민제, 효소제, 생균제, 향미제, 비단백태 질소 화합물(non-protein nitrogen compound: NPN), 규산염제, 완충제, 착색제, 추출제 또는 올리고당 등이 있으며, 이들은 단독으로 첨가되거나 또는 2종 이상이 함께 첨가될 수 있다.The feed additive containing the bacteriophage as an active ingredient may additionally include other additives as needed. Non-limiting examples of the additives that can be used include binders, emulsifiers, and preservatives added to prevent deterioration of feed quality; Amino acids, vitamins, enzymes, probiotics, flavoring agents, non-protein nitrogen compounds (NPN), silicate agents, buffers, colorants, extractants, or oligosaccharides added to increase the utility of feed include these. It may be added singly or two or more types may be added together.
상기 사료에 포함되는 박테리오파지 이외의 원료들은 당업계에서 통상적으로 사용되는 것으로 제한없이 사용될 수 있다. 상기 사료의 비제한적인 예로는, 곡물류, 근과류, 식품 가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류 또는 곡물 부산물류 등과 같은 식물성 사료; 단백질류, 무기물류, 유지류, 광물성류, 유지류, 단세포 단백질류, 동물성 플랑크톤류 또는 음식물 등과 같은 동물성 사료를 들 수 있다. 이들은 단독으로 사용되거나 2종 이상을 혼합하여 사용될 수 있다.Raw materials other than bacteriophages included in the feed are those commonly used in the industry and can be used without limitation. Non-limiting examples of the feed include plant feeds such as grains, roots and fruits, food processing by-products, algae, fiber, pharmaceutical by-products, oils and fats, starches, cucurbits or grain by-products; Examples include animal feeds such as proteins, inorganic substances, fats and oils, minerals, fats and oils, single-cell proteins, zooplanktons or foods. These may be used alone or in combination of two or more types.
상기 사료 첨가제, 사료는 당업계에서 통상적으로 사용되는 제조방법에 의해 제조될 수 있다.The feed additives and feeds can be manufactured by manufacturing methods commonly used in the industry.
상기 사료 첨가제, 사료는 이들의 품질 저하를 감소시키는데 충분한 유효량의 첨가제를 포함하는 것일 수 있고, 상기 첨가제는 보존제, 안정화제, 부형제 또는 동결보호제 등일 수 있다. 상기 사료 첨가제, 사료는 상기 첨가제를 포함함으로써, 자연 상태에 존재하는 박테리오파지와 다르게, 사료 첨가제, 사료 내에서 박테리오파지가 보다 오랜 기간 동안 생존하거나 활성이 유지되는 것일 수 있다. 상기 보존제, 안정화제, 부형제 또는 동결보호제는 사료 첨가제, 사료의 품질 저하를 감소시킬 수 있는 것이면, 당업계에서 통상적으로 사용되는 것들이 제한 없이 사용될 수 있다.The feed additive or feed may contain an effective amount of additive sufficient to reduce quality degradation, and the additive may be a preservative, stabilizer, excipient, or cryoprotectant. By containing the additive, the feed additive or feed may allow the bacteriophage to survive or remain active for a longer period of time in the feed additive or feed, unlike bacteriophages that exist in nature. The preservatives, stabilizers, excipients or cryoprotectants are feed additives and those commonly used in the art can be used without limitation as long as they can reduce the quality deterioration of the feed.
상기 목적을 달성하기 위한 또 다른 양태로서, 본 발명은 박테리오파지를 유효성분으로 포함하는 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환 예방 또는 치료용 약학적 조성물을 제공한다. 상기 용어 박테리오파지, 유효성분, 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환 등은 전술한 바와 같다.In another aspect for achieving the above object, the present invention provides a pharmaceutical composition for preventing or treating infectious diseases caused by Bacillus, Escherichia coli, or Salmonella, containing bacteriophage as an active ingredient. The terms bacteriophage, active ingredient, infectious disease caused by Bacillus, E. coli or Salmonella, etc. are as described above.
상기 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환의 예방 또는 치료용 약학적 조성물은 약학적으로 허용가능한 담체를 더 포함하는 것일 수 있고, 상기 담체와 함께 제제화되어 식품, 의약품, 사료 첨가제 또는 사료 등으로 제공될 수 있다.The pharmaceutical composition for preventing or treating infectious diseases caused by Bacillus, Escherichia coli, or Salmonella may further include a pharmaceutically acceptable carrier, and is formulated with the carrier to be used as food, medicine, feed additive, feed, etc. can be provided.
본 명세서에서 사용되는 용어, "약학적으로 허용가능한 담체"는 생물체를 자극하지 않고 투여 화합물의 생물학적 활성 및 특성을 저해하지 않는 담체 또는 희석제 등을 의미하는 것일 수 있다.As used herein, the term "pharmaceutically acceptable carrier" may mean a carrier or diluent that does not irritate living organisms and does not inhibit the biological activity and properties of the administered compound.
상기 조성물에 포함될 수 있는 담체의 종류는 특별히 제한되지 않으며, 당해 기술 분야에서 통상적으로 사용되고 약학적으로 허용가능한 담체라면 어느 것이든 사용될 수 있다. 상기 담체의 비제한적인 예로는, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사 용액, 덱스트로즈 용액, 말토덱스트린 용액, 글리세롤 등을 들 수 있다. 이들은 단독으로 사용되거나 2 종 이상을 혼합하여 사용될 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.The type of carrier that can be included in the composition is not particularly limited, and any carrier commonly used in the art and pharmaceutically acceptable can be used. Non-limiting examples of the carrier include saline solution, sterile water, Ringer's solution, buffered saline solution, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, etc. They can be used alone or in a mixture of two or more types, and other common additives such as antioxidants, buffers, and bacteriostatic agents can be added as needed. In addition, diluents, dispersants, binders, and lubricants can be additionally added to formulate injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets.
상기 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환의 예방 또는 치료용 약학적 조성물은 경구 투여 또는 비경구 투여를 통해 투여할 수 있으며, 질환 부위에의 도포 또는 분무하는 방법도 이용할 수 있다. 비경구 투여의 경우 정맥 내 투여, 복강 내 투여, 근육 내 투여, 피하 투여 또는 국부 투여를 이용하여 투여할 수도 있다. 상기 조성물의 적합한 도포, 분무 및 투여량은 제제화 방법, 투여 방식, 대상이 되는 동물 및 환자의 연령, 체중, 성, 질병 증상의 정도, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 민감성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사나 수의사는 목적하는 치료에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다.The pharmaceutical composition for preventing or treating infectious diseases caused by Bacillus, Escherichia coli, or Salmonella can be administered through oral or parenteral administration, and can also be applied or sprayed to the diseased area. In the case of parenteral administration, it may be administered using intravenous administration, intraperitoneal administration, intramuscular administration, subcutaneous administration, or local administration. Suitable application, spraying, and dosage of the composition are determined by factors such as formulation method, administration method, age, weight, sex, degree of disease symptoms, food, administration time, administration route, excretion rate, and reaction sensitivity of the subject animal and patient. It varies depending on factors, and usually a skilled doctor or veterinarian can easily determine and prescribe an effective dosage for the desired treatment.
상기 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환의 예방 또는 치료용 약학적 조성물의 경구 투여용 제형으로는, 예를 들어 정제, 트로키제, 로젠지(lozenge), 수용성 또는 유성 현탁액, 조제분말 또는 과립, 에멀젼, 하드 또는 소프트 캡슐, 시럽 또는 엘릭시르제로 제제화할 수 있다. 정제 및 캡슐 등의 제형으로 제제화하기 위해, 락토오스, 사카로오스, 솔비톨, 만니톨, 전분, 아밀로펙틴, 셀룰로오스 또는 젤라틴과 같은 결합제, 디칼슘 포스페이트와 같은 부형제, 옥수수 전분 또는 고구마 전분과 같은 붕괴제, 스테아르산 마그네슘, 스테아르산 칼슘, 스테아릴푸마르산 나트륨 또는 폴리에틸렌글리콜 왁스와 같은 윤활유를 포함할 수 있으며, 캡슐 제형의 경우 상기 언급한 물질 외에도 지방유와 같은 액체 담체를 더 함유할 수 있다.Formulations for oral administration of the pharmaceutical composition for preventing or treating infectious diseases caused by Bacillus, Escherichia coli, or Salmonella include, for example, tablets, troches, lozenges, water-soluble or oily suspensions, prepared powders, or It can be formulated as granules, emulsions, hard or soft capsules, syrups, or elixirs. For formulation into dosage forms such as tablets and capsules, binders such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose or gelatin, excipients such as dicalcium phosphate, disintegrants such as corn starch or sweet potato starch, and magnesium stearate. , may contain a lubricant such as calcium stearate, sodium stearyl fumarate, or polyethylene glycol wax, and in the case of a capsule formulation, it may further contain a liquid carrier such as fatty oil in addition to the above-mentioned substances.
상기 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환의 예방 또는 치료용 약학적 조성물의 비경구 투여용 제형으로는, 피하주사, 정맥주사 또는 근육내 주사 등의 주사용 형태, 좌제 주입방식 또는 호흡기를 통하여 흡입이 가능하도록 하는 에어로졸제 등 스프레이용으로 제제화할 수 있다. 주사용 제형으로 제제화하기 위해서는 본 발명의 조성물을 안정화제 또는 완충제와 함께 물에서 혼합하여 용액 또는 현탁액으로 제조하고, 이를 앰플 또는 바이알의 단위 투여용으로 제제화할 수 있다. 에어로졸제 등의 스프레이용으로 제형화하는 경우, 수분산된 농축물 또는 습윤 분말이 분산되도록 추진제 등이 첨가제와 함께 배합될 수 있다.Formulations for parenteral administration of the pharmaceutical composition for preventing or treating infectious diseases caused by Bacillus, Escherichia coli, or Salmonella include injection forms such as subcutaneous injection, intravenous injection, or intramuscular injection, suppository injection, or respiratory tract injection. It can be formulated as a spray, such as an aerosol that allows inhalation. In order to formulate a dosage form for injection, the composition of the present invention can be mixed in water with a stabilizer or buffer to prepare a solution or suspension, and the composition can be formulated for unit administration in ampoules or vials. When formulating for spraying, such as an aerosol, a propellant, etc. may be mixed with additives to disperse the water-dispersed concentrate or wet powder.
상기 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환의 예방 또는 치료용 약학적 조성물은 보존제, 안정화제, 습윤제, 유화제, 동결보호제(cryoprotectant) 또는 부형제 등을 포함할 수 있다.The pharmaceutical composition for preventing or treating infectious diseases caused by Bacillus, E. coli, or Salmonella may include a preservative, stabilizer, wetting agent, emulsifier, cryoprotectant, or excipient.
상기 보존제, 안정화제 또는 부형제는 상기 조성물의 품질 저하(deterioration)를 감소시키는데 충분한 유효량으로 조성물에 포함되는 것일 수 있다.The preservative, stabilizer, or excipient may be included in the composition in an effective amount sufficient to reduce deterioration of the composition.
본 명세서에서 사용되는 용어, "품질 저하"는 조성물 등에 포함되는 박테리오파지의 균 수 감소, 활성 감소, 또는 이들의 조합을 포함하는 것일 수 있다.As used herein, the term "deterioration in quality" may include a reduction in the number of bacteria, a reduction in activity, or a combination thereof of bacteriophages included in a composition.
예를 들어, 상기 조성물은 조성물의 품질 저하를 감소시키는데 충분한 유효량의 보존제, 안정화제 또는 부형제를 포함함으로써 자연 상태에 존재하는 박테리오파지와 다르게 조성물 내에서 박테리오파지 LBC1이 보다 오랜 기간 동안 생존하거나 활성이 유지되는 것일 수 있다.For example, the composition may contain an effective amount of a preservative, stabilizer, or excipient sufficient to reduce degradation of the composition, thereby allowing bacteriophage LBC1 to survive or maintain activity for a longer period of time in the composition, unlike bacteriophages that exist in nature. It may be.
상기 보존제, 안정화제 또는 부형제는 상기 조성물의 품질 저하를 감소시킬 수 있는 것이라면, 당업계에서 통상적으로 사용되는 것들이 제한 없이 사용될 수 있다. 예를 들어 상기 안정화제는 알긴산염(alginate), 알긴산 나트륨(sodium alginate), 카제인, 카제인 나트륨, 셀룰로스, 메틸셀룰로스, 카르복시메틸셀룰로스 (carboxymethylcellulose), 카르복시메틸셀룰로스 나트륨(sodium carboxymethylcellulose), 펙틴, 젤라틴, 아라비아검, 잔탄검, 덱스트란, 사이클로덱스트린 및 전분으로 구성되는 군으로부터 선택되는 어느 하나 이상일 수 있다.The preservatives, stabilizers or excipients may be those commonly used in the art without limitation, as long as they can reduce quality degradation of the composition. For example, the stabilizer includes alginate, sodium alginate, casein, sodium caseinate, cellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, pectin, gelatin, It may be any one or more selected from the group consisting of gum arabic, xanthan gum, dextran, cyclodextrin, and starch.
상기 동결보호제는 상기 조성물이 동결건조된 상태일 때, 조성물의 품질 저하를 감소시키는데 충분한 유효량으로 조성물에 포함되는 것일 수 있다. 예를 들어 동결건조된 조성물 내에서 활성이 저하되거나 생존할 수 없는 자연 상태에 존재하는 박테리오파지와 다르게, 상기 조성물은 동결건조된 상태에서 조성물의 품질 저하를 감소시키는데 충분한 유효량의 동결보호제를 포함함으로써 동결건조된 조성물 내에서도 박테리오파지 활성이 유지되거나 박테리오파지가 생존할 수 있는 것일 수 있다.The cryoprotectant may be included in the composition in an effective amount sufficient to reduce quality degradation of the composition when the composition is freeze-dried. For example, unlike bacteriophages that exist in a natural state where their activity is reduced or cannot survive in a lyophilized composition, the composition is frozen by containing an effective amount of a cryoprotectant sufficient to reduce degradation of the composition in the lyophilized state. Even in the dried composition, bacteriophage activity may be maintained or bacteriophages may be able to survive.
상기 동결보호제는 동결건조된 상태인 조성물의 품질 저하를 감소시키기 위한 것이라면, 당업계에서 통상적으로 사용되는 것들이 제한 없이 사용될 수 있다. 예를 들어 상기 동결보호제는 글리세롤, 에틸렌 글리콜, 프로필렌 글리콜, 디메틸설폭시드(dimethyl sulfoxide: DMSO), 글루코스, 트레할로스, 말토덱스트린, 덱스트린, 스킴밀크 및 전분으로 구성되는 군으로부터 선택되는 어느 하나 이상일 수 있다.As long as the cryoprotectant is intended to reduce quality degradation of the freeze-dried composition, those commonly used in the art may be used without limitation. For example, the cryoprotectant may be one or more selected from the group consisting of glycerol, ethylene glycol, propylene glycol, dimethyl sulfoxide (DMSO), glucose, trehalose, maltodextrin, dextrin, skim milk, and starch. .
상기 목적을 달성하기 위한 또 다른 양태로서, 본 발명은 상기 박테리오파지를 대상에 처리하는 단계를 포함하는, 세균 살균 방법을 제공한다.As another aspect for achieving the above object, the present invention provides a method of bacterial sterilization, comprising the step of treating the subject with the bacteriophage.
구체적으로, 상기 세균을 살균하는 방법은 본 발명의 박테리오파지를 유효성분으로 포함하는 소독제 또는 세척제의 유효량을 세균에 처리하는 단계를 포함할 수 있으나, 이에 제한되는 것은 아니다.Specifically, the method of sterilizing bacteria may include treating the bacteria with an effective amount of a disinfectant or detergent containing the bacteriophage of the present invention as an active ingredient, but is not limited thereto.
본 명세서에서 사용되는 용어 "살균"은 박테리오파지를 이용해 세균을 죽이는 것으로, 상기 세균은 바실러스균, 대장균 또는 살모넬라균을 의미하나 이에 한정되는 것은 아니다.The term "sterilization" used in this specification refers to killing bacteria using bacteriophages, and the bacteria refers to Bacillus, Escherichia coli, or Salmonella, but is not limited thereto.
본 명세서에서 사용되는 용어 "대상"은 바실러스균, 대장균 또는 살모넬라균에 노출되었거나 노출될 가능성이 있는 식품, 동물의 피부 표면, 신체 각 부위 뿐만 아니라 동물의 활동 영역, 도축장, 폐사 지역, 조리 장소 또는 조리 설비 등이 대상이 될 수 있으나 이에 한정되는 것은 아니다.The term "object" used in this specification refers to food exposed or likely to be exposed to Bacillus, E. coli, or Salmonella, the skin surface of animals, each body part, as well as the animal's activity area, slaughterhouse, death area, and cooking. The target may be a location or cooking equipment, but is not limited to this.
본 발명의 신규 박테리오파지는 바실러스균, 대장균 또는 살모넬라균 생육 억제 또는 사멸능이 있으므로, 이를 항생제, 소독제, 세척제, 식품 첨가제, 식품, 사료 첨가제, 사료, 바실러스균, 대장균 또는 살모넬라균으로 인한 감염성 질환 예방 또는 치료용 약학적 조성물 등에 널리 활용할 수 있다.The new bacteriophage of the present invention has the ability to inhibit or kill the growth of Bacillus, E. coli, or Salmonella, and therefore can be used as an antibiotic, disinfectant, detergent, food additive, food, feed additive, feed, or to prevent infectious diseases caused by Bacillus, E. coli, or Salmonella. It can be widely used in therapeutic pharmaceutical compositions, etc.
도 1은 본 발명에서 분리한 박테리오파지 LBC1이 형성하는 플라크(plaque)를 나타낸 사진이다.
도 2는 본 발명에서 분리한 박테리오파지 LBC1의 시간 경과(총 20시간)에 따른 숙주 용균 활성을 나타내는 그래프이다.
도 3은 본 발명에서 분리한 박테리오파지 LBC1의 시간 경과(총 84시간)에 따른 숙주 용균 활성을 나타내는 그래프이다.Figure 1 is a photograph showing a plaque formed by bacteriophage LBC1 isolated in the present invention.
Figure 2 is a graph showing the host lytic activity of the bacteriophage LBC1 isolated in the present invention over time (total 20 hours).
Figure 3 is a graph showing the host lytic activity of the bacteriophage LBC1 isolated in the present invention over time (total 84 hours).
이하, 실시예를 통하여 본 발명의 구성 및 효과를 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것일 뿐, 본 발명의 범위가 이에 의해 한정되는 것은 아니다.Hereinafter, the configuration and effects of the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.
실시예 1: 박테리오파지 LBC1의 분리Example 1: Isolation of bacteriophage LBC1
전북 김제시 공공하수처리시설에서 하수 샘플을 채취하고, 50mL 튜브에 하수 샘플 20ml과 2배 농축된 TSB 배지 20ml, 2mM CaCl2, 숙주가 되는 바실러스 세레우스 균주 (B. cereus ATCC 11778) 배양액을 넣고 30℃에서 16시간 배양하였다.A sewage sample was collected from a public sewage treatment facility in Gimje-si, Jeollabuk-do, and 20 ml of sewage sample, 20 ml of twice-concentrated TSB medium, 2mM CaCl 2 , and the culture medium of the host Bacillus cereus strain (B. cereus ATCC 11778) were added to a 50 mL tube. Cultured for 16 hours at ℃.
증식된 배양액은 원심분리 후 여과시켜(0.45μm) 샘플 중 이물과 세균을 제거하였다. 12시간 이상 배양한 바실러스균을 Top Agar(0.4%)와 섞어 1.5% Agar 배지에 부어 굳힌 후, 상기 증식 샘플 10μl을 떨어뜨리고, 30℃에서 16시간 동안 배양하였다.The grown culture was centrifuged and filtered (0.45 μm) to remove foreign substances and bacteria from the sample. Bacillus bacteria cultured for more than 12 hours were mixed with Top Agar (0.4%) and poured into 1.5% Agar medium to solidify. Then, 10 μl of the growth sample was added and cultured at 30°C for 16 hours.
목적하는 박테리오파지가 플레이트 상에 나타난 경우, 독립되고 투명한 플라크(plaque)가 관찰되었다 (도 1). 이 플라크 영역을 팁을 이용하여 분리해 낸 다음, 새로운 박테리아 배양액에 넣었는데, 배양액이 맑아짐을 관찰할 수 있었다.When the desired bacteriophage appeared on the plate, independent and transparent plaques were observed (Figure 1). This plaque area was separated using a tip and then placed in a new bacterial culture, and it was observed that the culture fluid became clear.
그 후에 배양액을 원심분리한 후, 상층액만을 취해 박테리오파지만을 포함하는 여과액을 회수할 수 있었다. 염화세슘(CsCl) 밀도차를 이용한 초고속 원심분리를 통해 회수된 박테리오파지 여과액으로 부터 순수한 박테리오파지를 얻을 수 있었다.Afterwards, the culture medium was centrifuged, and only the supernatant was taken to recover a filtrate containing only bacteriophages. Pure bacteriophages were obtained from the bacteriophage filtrate recovered through ultra-high-speed centrifugation using cesium chloride (CsCl) density difference.
이와 같이 얻은 박테리오파지는 바실러스 세레우스에 대한 사멸효과가 우수하고, 특히 오랜 시간이 지난 후에도 저항성 세균이 나타나는 비율이 적어 사멸효과가 우수하며, 이를 LBC1로 명명하고, 한국생명공학연구원에 기탁하여 기탁번호 KCTC 15078BP를 부여받았다.The bacteriophage obtained in this way has an excellent killing effect against Bacillus cereus, and in particular, the rate of resistant bacteria appearing even after a long period of time is low, so the killing effect is excellent. It was named LBC1 and deposited at the Korea Research Institute of Bioscience and Biotechnology, with accession number Received KCTC 15078BP.
실시예 2: 수득한 파지의 염기서열 분석Example 2: Base sequence analysis of the obtained phage
분리한 파지의 염기서열 분석을 위하여 파지 유전자를 분리하였다. 순수 분리된 박테리오파지 1 mL에 0.5 M EDTA(pH 8.0), 프로테이나아제(proteinase) K, SDS를 첨가하되, 시약을 첨가한 후의 농도가 각각 20 mM, 50μg/mL, 0.5%가 되도록 하였다. 혼합된 용액은 2시간 동안 56℃로 온도를 유지하며 이후 상온에서 식혔다. 동량의 페놀을 넣고 3000g 에서 5분 동안 원심분리 하였으며, 상층액만을 얻어 PCI(phenol-chloroform-isoamylalcohol)를 다시 한 번 처리하고, 동일한 조건의 원심분리를 수행하였다. 위에서 획득한 상층액에 동량의 클로로포름(chloroform)을 첨가하여 원심분리하였다. 이 과정을 반복하고 95% 에탄올 1 mL과 3 M 소디움 아세테이트(Sodium acetate, pH 5.2)를 100μL 첨가하여 -80℃에서 DNA를 침전시킨 뒤 15분 동안 원심분리한 후, 70% 에탄올을 첨가하여 한번 더 원심분리하였다. 에탄올을 제거하고 DNA를 건조시킨 후, 증류수에 DNA를 녹였다.To analyze the base sequence of the isolated phage, the phage genes were isolated. 0.5 M EDTA (pH 8.0), proteinase K, and SDS were added to 1 mL of pure isolated bacteriophage, and the concentrations after addition of the reagents were 20 mM, 50 μg/mL, and 0.5%, respectively. The mixed solution was kept at 56°C for 2 hours and then cooled to room temperature. The same amount of phenol was added and centrifuged at 3000g for 5 minutes. Only the supernatant was obtained, treated again with PCI (phenol-chloroform-isoamylalcohol), and centrifuged under the same conditions. An equal amount of chloroform was added to the supernatant obtained above and centrifuged. Repeat this process, add 1 mL of 95% ethanol and 100 μL of 3 M sodium acetate (pH 5.2) to precipitate DNA at -80°C, centrifuge for 15 minutes, and add 70% ethanol once. Further centrifugation was performed. After removing the ethanol and drying the DNA, the DNA was dissolved in distilled water.
순수 분리된 총 유전자의 염기서열을 결정하였으며, 박테리오파지 LBC1의 염기서열은 총 155,058bp (서열번호 1) 크기이며, 상기 염기서열은 서열번호 1에 나타내었다. 결정된 염기서열을 'RAST(Rapid Annotation using Subsystem Technology)' 프로그램을 이용하여 분석하였다. 분석한 결과, LBC1의 유전체(genome)에서 219개의 오픈 리딩 프레임(open reading frame, ORFs)과 20개의 tRNA가 예측되었고, 이중 180개의 ORF는 아직 기능이 밝혀지지 않은 가정적인 단백질(hypothetical protein)로 판단된다.The nucleotide sequence of the total pure isolated gene was determined, and the nucleotide sequence of bacteriophage LBC1 has a total size of 155,058 bp (SEQ ID NO. 1), and the nucleotide sequence is shown in SEQ ID NO. 1. The determined base sequence was analyzed using the 'RAST (Rapid Annotation using Subsystem Technology)' program. As a result of the analysis, 219 open reading frames (ORFs) and 20 tRNAs were predicted in the LBC1 genome, of which 180 ORFs were hypothetical proteins whose functions have not yet been discovered. It is judged.
39개의 ORF는 크게 대사(metabolism), 패키징(packaging), 구조(sturcutre), 용균 (lysis) 등의 4개의 집단으로 나뉠 수 있다. 박테리오파지를 용원상태로 유지시키는 인테그레이즈(integrase)나 리프레서(repressor) 등은 예측되지 않았으므로 LBC1이 용균성 파지임을 재확인하였다. LBC1의 유전자의 추정되는 기능은 하기 표 1에 나타내었다.The 39 ORFs can be broadly divided into four groups: metabolism, packaging, structure, and lysis. Since the integrase or repressor that maintains the bacteriophage in a lysogenic state was not predicted, it was confirmed again that LBC1 is a lytic phage. The putative functions of the LBC1 genes are shown in Table 1 below.
실험예 1: 박테리오파지 LBC1의 바실러스균 용균성 분석Experimental Example 1: Analysis of Bacillus lytic activity of bacteriophage LBC1
숙주 B. cereus ATCC 11778 배양액에 일정 농도의 박테리오파지 LBC1을 섞고 일정 시간마다 흡광도를 측정하여 대조군과 비교함으로써 LBC1의 숙주 용균 능력을 확인하였다. Host B. cereus ATCC 11778 The host lytic ability of LBC1 was confirmed by mixing a certain concentration of bacteriophage LBC1 into the culture medium and measuring the absorbance at regular intervals and comparing it with the control group.
바실러스 세레우스만을 배양한 대조군에 비해 바실러스 세레우스에 박테리오파지 LBC1을 섞은 경우, 흡광도가 현저하게 감소하여 박테리오파지 LBC1이 바실러스 세레우스에 대해 용균 효과가 우수함을 확인하였다(도 2).Compared to the control group in which only Bacillus cereus was cultured, when Bacillus cereus was mixed with bacteriophage LBC1, the absorbance was significantly reduced, confirming that bacteriophage LBC1 had an excellent lytic effect on Bacillus cereus (Figure 2).
또한 박테리오파지 LBC1을 처리한 후 84시간이 지나도 대조군에 비해 현저히 적은 흡광도 값을 유지하고 있음을 확인하였다. 일반적으로 박테리오파지를 숙주 세균 배양액에 감염시키면 일정시간 경과 후 파지에 저항성을 가지는 숙주 세균이 급격히 발생하는 것으로 알려져 있으나, LBC1을 처리하면 시간이 경과하여도 LBC1에 대한 저항성을 가지는 바실러스 세레우스균이 거의 나타나지 않았다. 이는 LBC1이 일반적인 박테리오파지 보다 숙주 세균에 대한 사멸효과가 강하다는 것을 나타내는 결과이다(도 3).In addition, it was confirmed that the absorbance value was maintained significantly lower than that of the control group even 84 hours after treatment with bacteriophage LBC1. In general, it is known that when a bacteriophage is infected in a host bacterial culture, host bacteria resistant to the phage rapidly develop after a certain period of time, but when treated with LBC1, almost no Bacillus cereus bacteria that are resistant to LBC1 are present even over time. didn't show up This result indicates that LBC1 has a stronger killing effect on host bacteria than general bacteriophages (Figure 3).
실험예 2: 박테리오파지 LBC1의 숙주 특이성 분석Experimental Example 2: Analysis of host specificity of bacteriophage LBC1
박테리오파지 LBC1의 숙주 특이성을 확인하기 위해 분리균인 바실러스 세레우스를 포함한 식중독 세균에 대한 용균 활성을 분석하였다.To confirm the host specificity of bacteriophage LBC1, its lytic activity against food poisoning bacteria, including the isolate Bacillus cereus, was analyzed.
박테리오파지 LBC1의 숙주 특이성은 적하법(Dropping method)을 통해 결정하였다. 16시간 배양된 세균 배양액과 0.4%의 agar 배지를 섞은 후, 1.5% Agar 배지에 부어서 상온에서 15분간 건조하였고, 그 위에 파지 배양액을 떨어뜨리고, 30℃에서 16시간 정치 배양시켰다. 균주가 파지에 대해 감수성을 갖는 경우, 플래이트상에 투명한 영역, 즉 플라그(plaque)를 보이는데, 이는 세균 세포가 완전하게 용해(lysis)된 결과임을 증명하는 것이다. 만약 감수성이 약한 경우는 뿌연 영역이 생기거나, 독립적인 볼드 스팟이 나타난다.The host specificity of bacteriophage LBC1 was determined through the dropping method. After mixing the bacterial culture cultured for 16 hours with 0.4% agar medium, it was poured into 1.5% agar medium and dried at room temperature for 15 minutes. The phage culture medium was dropped on top of it and incubated for 16 hours at 30°C. If the strain is susceptible to phage, a transparent area, that is, a plaque, appears on the plate, which proves that it is the result of complete lysis of the bacterial cells. If sensitivity is weak, hazy areas may appear or independent bold spots may appear.
실험 결과, 본 발명의 박테리오파지 LBC1는 바실러스 세레우스 외에 바실러스 마이코이데스(Bacillus mycoides), 바실러스 파라마이코이데스(Bacillus paramycoides) 및 바실러스 투린지엔시스(Bacillus thuringiensis) 등 바실러스 속(Bacillus sp.)에 속하는 균주 등에 용해 활성을 보였다. 특히 바실러스 세레우스 분리 균주 중 비교적 항생제 내성이 높은 분리균 31 균주에 대해 용균 활성을 측정했을 때, 21 균주에 대해 사멸효과를 보이므로 항생제 내성 균주에 대한 약 68% 용해 활성을 나타냈다.As a result of the experiment, the bacteriophage LBC1 of the present invention belongs to the genus Bacillus ( Bacillus sp .), such as Bacillus mycoides, Bacillus paramycoides , and Bacillus thuringiensis, in addition to Bacillus cereus. It showed lytic activity on strains, etc. In particular, when the lytic activity was measured for 31 strains of Bacillus cereus isolates with relatively high antibiotic resistance, it showed a killing effect on 21 strains, showing about 68% lytic activity against antibiotic-resistant strains.
이외에도 크로노박터 사카자키, 리스테리아 모노사이토제네스, 황생포도상구균, 비브리오균 등에는 효과가 없었으나 대장균 11균주 중 7균주, 살모넬라균 5균주 중 5균주에 대한 용균 활성을 보였다. In addition, it was not effective against Cronobacter sakazakii, Listeria monocytogenes, Staphylococcus aureus, and Vibrio bacteria, but showed lytic activity against 7 out of 11 E. coli strains and 5 out of 5 Salmonella strains.
용해 활성을 플라그의 투명도에 따라 3단계로 나누어 박테리오파지 LBC1의 용균 활성을 표 2에 나타내었다[+++ : 맑게 용균(clear lysis), ++ : 약간 탁함(turbid), + : 매우 탁함(very turbid), - : 비용균(no lysis)].The lytic activity of bacteriophage LBC1 was divided into three stages according to the transparency of the plaque, and the lytic activity of bacteriophage LBC1 is shown in Table 2 [+++: clear lysis, ++: slightly turbid, +: very turbid. turbid), -: nasal bacteria (no lysis)].
서열목록 전자파일 첨부Sequence list electronic file attached
Claims (16)
상기 박테리오파지는 KCTC 15078BP로 기탁된 박테리오파지. In paragraph 1
The bacteriophage is a bacteriophage deposited as KCTC 15078BP.
상기 바실러스균은 바실러스 세레우스(Bacillus cereus), 바실러스 마이코이데스(Bacillus mycoides), 바실러스 파라마이코이데스(Bacillus paramycoides) 및 바실러스 투린지엔시스(Bacillus thuringiensis)로부터 선택된 1종 이상인 것인, 박테리오파지.According to paragraph 1,
The Bacillus bacterium is one or more types selected from Bacillus cereus, Bacillus mycoides , Bacillus paramycoides , and Bacillus thuringiensis. A bacteriophage.
상기 살모넬라균은 살모넬라 엔테리티디스(Salmonella enteritidis) 및 살모넬라 티피무리움(Salmonella typhimurium)으로부터 선택된 1종 이상인 것인, 박테리오파지.According to paragraph 1,
The Salmonella bacteriophage is one or more types selected from Salmonella enteritidis and Salmonella typhimurium.
상기 바실러스균, 대장균 또는 살모넬라균에 의한 감염성 질환은 바실러스 세레우스 감염증, 식중독, 대장균 감염증, 출혈성 대장염, 요독증후군, 혈소판 감소성 자반증, 살모넬라균 감염증, 또는 장티푸스인 것인, 조성물.According to clause 13,
The composition, wherein the infectious disease caused by Bacillus, E. coli, or Salmonella is Bacillus cereus infection, food poisoning, E. coli infection, hemorrhagic colitis, uremic syndrome, thrombocytopenic purpura, Salmonella infection, or typhoid fever.
세균 살균 방법.Comprising the step of processing the bacteriophage of paragraph 1 on the target,
How to sterilize bacteria.
상기 세균은 바실러스균, 대장균 또는 살모넬라균인 것인, 살균 방법.
According to clause 15,
A sterilization method wherein the bacteria are Bacillus, E. coli, or Salmonella.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/KR2023/016794 WO2024091038A1 (en) | 2022-10-28 | 2023-10-26 | Novel bacteriophages lbc1, lbc2, lec1, lec2, or lse1 and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20240066489A true KR20240066489A (en) | 2024-05-16 |
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