Novel bacteriophage having specific killing ability against salmonella enterica and antibacterial composition comprising same

Abstract

The present invention relates to a novel bacteriophage having specific killing ability against Salmonella enterica and an antibacterial composition comprising same, wherein the composition comprising the bacteriophage as an active ingredient can be usefully employed as a composition for preventing or treating infectious diseases caused by Salmonella enterica, feed for livestock, drinking water, a cleaning agent, and a disinfectant.

Description

Novel bacteriophage having specific killing ability against Salmonella enterica and antibacterial composition comprising the same

[0001] The present invention relates to a novel bacteriophage having a specific killing ability against Salmonella enterica and an antibacterial composition comprising the same.

[0002] Salmonella is a genus of Gram-negative, usually anaerobic bacteria belonging to the Enterobacteriaceae family. It is a non-spore-forming rod-shaped bacterium, typically motile via a trichome flagellum. Salmonella species are pathogenic microorganisms that infect not only humans but also various livestock, causing various diseases.

[0003] According to statistics from the U.S. Centers for Disease Control and Prevention (CDC), Salmonella accounted for 16% of human foodborne illnesses between 2005 and 2008. Furthermore, a 2002 risk assessment conducted by the FAO and WHO reported that the incidence of Salmonella foodborne illness transmitted through eggs and poultry was closely related to the prevalence of Salmonella in poultry. This suggests that a decrease in the prevalence of Salmonella in poultry will also lead to a decrease in the incidence of Salmonella foodborne illness in humans.

[0004] Recent food safety concerns have been raised by illnesses caused by Salmonella bacteria, which come not only from livestock but also from a variety of food ingredients used in cookie dough, including peanuts, spinach, tomatoes, and peppers.

[0005] Likewise, due to the damage caused by Salmonella, reporting of Salmonella infections is mandatory in Germany. Furthermore, in the United States, approximately 40,000 cases of Salmonella infection are reported annually.

[0006] Therefore, there is a need to find ways to control salmonellosis in livestock and Salmonella enterica, which can cause salmonella food poisoning in humans from livestock origin.

[0007] Meanwhile, bacteriophages are bacteria-specific viruses that infect only certain bacteria and control their growth. They are often abbreviated as "phages." Bacteriophages consist of single- or double-stranded DNA or RNA as their genetic material, forming a nucleic acid. This nucleic acid is surrounded by a protein coat, and has a simple structure. It is divided into three basic structures: an icosahedral head with a tail, an icosahedral head without a tail, and a filamentous form.

[0008] Bacteriophages, which have an icosahedral head and a tail, the most common structure, can be subdivided into Myoviridae with contractile tails, Siphoviridae with long, non-contractile tails, and Podoviridae with short tails. Bacteriophages with an icosahedral head and no tail are subdivided into the shape of the head, its composition, and the presence or absence of an envelope. Finally, filamentous bacteriophages are subdivided into the size, shape, and composition of the envelope and filaments. These bacteriophages cannot replicate independently of a bacterial host.

[0009] When infecting bacteria, bacteriophages attach to the bacterial surface, inject their genetic material into the cell, and then become either lytic or lysogenic. Lytic bacteriophages destroy or lyse the cell by using cellular machinery to form their own structures and then releasing new bacteriophage particles. Lysogenic bacteriophages replicate along with the bacterial host cell without destroying it by incorporating their nucleic acid into the bacterial host cell's chromosome. However, under certain conditions, they become lytic.

[0010] Since the discovery of these bacteriophages, research has focused on using them as treatments for infectious diseases. However, most bacteriophage research has focused on controlling Escherichia coli, Listeria monocytogenes, and Clostridium spp. As mentioned above, the damage caused by Salmonella continues unabated, and its resistance to multiple drugs is high. Therefore, the development of bacteriophages capable of controlling Salmonella is urgently needed.

[0011] Against this backdrop, the inventors of the present invention conducted extensive research to select a bacteriophage capable of selectively killing Salmonella enterica bacteria, and as a result, isolated and identified a novel bacteriophage targeting Salmonella enterica bacteria from the stool of infants and toddlers, and confirmed that a composition containing the bacteriophage can effectively prevent, treat, and control the proliferation of Salmonella bacteria, thereby completing the present invention.

[0012] [Prior Art Literature]

[0013] [Patent Document]

[0014] (Patent Document 1) Korean Patent Registration No. KR 10-2009174

[0015] The purpose of the present invention is to provide a bacteriophage having the ability to specifically kill Salmonella enterica bacteria and deposited under the accession number KCTC 15560BP.

[0016] Another object of the present invention is to provide a composition for preventing or treating an infectious disease caused by Salmonella enterica, comprising the bacteriophage as an active ingredient.

[0017] Another object of the present invention is to provide a method for preventing or treating an infectious disease caused by Salmonella enterica bacteria, comprising a step of administering to a subject a composition containing the bacteriophage as an active ingredient.

[0018] Another object of the present invention is to provide an antibiotic comprising the bacteriophage as an active ingredient.

[0019] Another object of the present invention is to provide livestock feed or drinking water containing the bacteriophage as an active ingredient.

[0020] Another object of the present invention is to provide a disinfectant or detergent containing the bacteriophage as an active ingredient.

[0021] The advantages and features of the present invention, and the methods for achieving them, will become clearer with reference to the embodiments described in detail below together with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below and may be implemented in various different forms. These embodiments are provided solely to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the present invention, and the present invention is defined solely by the scope of the claims.

[0022] The terminology used herein is for the purpose of describing embodiments only and is not intended to limit the present invention. In this specification, the singular also includes the plural unless specifically stated otherwise. As used herein, the terms "comprises" and / or "comprising" do not exclude the presence or addition of one or more other components in addition to the mentioned components. Like reference numerals refer to like components throughout the specification, and "and / or" includes each and any combination of one or more of the mentioned components. Although "first", "second", etc. are used to describe various components, these components are not limited by these terms. These terms are only used to distinguish one component from another. Therefore, it should be understood that a first component mentioned below may also be a second component within the technical spirit of the present invention.

[0023] Unless otherwise defined, all terms (including technical and scientific terms) used herein may be used in their common sense to those skilled in the art to which the present invention pertains. Furthermore, terms defined in commonly used dictionaries are not to be interpreted ideally or excessively unless explicitly and specifically defined otherwise.

[0024] The present invention provides a bacteriophage having the ability to specifically kill Salmonella enterica bacteria and deposited under the accession number KCTC 15560BP.

[0025] The bacteriophage of the present invention is a bacteria-specific virus that infects a specific bacterium and inhibits and suppresses the growth of the bacterium, and refers to a virus containing single or double-stranded DNA or RNA as genetic material.

[0026] The bacteriophage of the present invention was deposited by the inventors at the Biological Resource Center of the Korea Research Institute of Bioscience and Biotechnology on August 18, 2023, under the deposit number KCTC 15560BP. In a specific embodiment of the present invention, the inventors selected a bacteriophage having a specific killing ability against Salmonella enterica and deposited the isolated bacteriophage at the Korea Research Institute of Bioscience and Biotechnology.

[0027] The bacteriophage of the present invention may have acid resistance in the range of pH 3 to 11 and heat resistance in the range of 37 to 70°C.

[0028] The bacteriophage of the present invention can be used to regulate, inhibit or control the growth, division and colonization of Salmonella enterica bacteria.

[0029] In addition, the present invention provides a composition for preventing or treating an infectious disease caused by Salmonella enterica, comprising the bacteriophage as an active ingredient.

[0030] The composition comprising the bacteriophage of the present invention can be manufactured in various forms according to specific purposes in the household, industrial, medical and environmental fields. For example, it can be manufactured in a liquid form, a spray form or a solid form containing an amount of bacteriophage effective for preventing, controlling, inhibiting and / or controlling the growth, aggregation and division of Salmonella enterica for cleaning of living organisms as well as various equipment and instruments, and may include additional components such as surfactants, detergents, bactericides, fungicides, acidity regulators, dyes and pigments depending on the purpose, but is not limited thereto.

[0031] The composition comprising the above bacteriophage may include a pharmaceutical composition comprising the bacteriophage as an active ingredient.

[0032] The bacteriophage of the present invention specifically kills Salmonella enterica, and thus can be useful for treating, alleviating symptoms, preventing, and / or suppressing various diseases caused by Salmonella enterica. Examples of such diseases include, but are not limited to, food poisoning, inflammation, and typhoid fever caused by Salmonella enterica.

[0033] Pharmaceutically acceptable carriers included in the pharmaceutical composition of the present invention are those commonly used in formulations, and include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like.

[0034] The pharmaceutical composition of the present invention can be used by applying or spraying to a diseased area, and can also be administered through oral or parenteral administration. In the case of parenteral administration, it can be administered through intravenous administration, intraperitoneal administration, intramuscular administration, subcutaneous administration, or local administration.

[0035] The suitable application, spraying and dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, administration method, age, body weight, sex, degree of disease symptoms, food, administration time, administration route, excretion rate and response sensitivity of the target animal and patient, and a skilled doctor or veterinarian can easily determine and prescribe an effective dosage for the desired treatment. Generally, the pharmaceutical composition of the present invention is about 1 × 10 5 1 × 10 15 It can be administered at a concentration of PFU / ml.

[0036] The pharmaceutical composition of the present invention may be manufactured in a unit dosage form or may be manufactured by inserting it into a multi-dose container by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method that can be easily performed by a person having ordinary skill in the art to which the present invention pertains. In this case, the formulation may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, or in the form of an extract, powder, granules, tablet or capsule, and may additionally include a dispersing agent or stabilizer.

[0037] In addition, the present invention provides a method for preventing or treating an infectious disease caused by Salmonella enterica bacteria, comprising a step of administering to a subject a composition containing the bacteriophage as an active ingredient.

[0038] The infectious disease caused by the Salmonella enterica bacteria of the present invention may be, but is not limited to, salmonellosis or salmonella food poisoning.

[0039] Administration of the present invention refers to introducing a predetermined substance to a subject by an appropriate method.

[0040] The subject of the present invention includes, but is not limited to, mammals, livestock, or poultry, including humans, that have developed or are capable of developing a disease. The livestock refers to useful animals that have been domesticated and improved by humans and coexist with humans, and includes, but is not limited to, pigs, cows, chickens, horses, ducks, or dogs, for example. The poultry refers to animals belonging to the avian group among livestock, and includes, but is not limited to, pheasants, quails, ostriches, geese, or turkeys, for example.

[0041] In addition, the present invention provides an antibiotic comprising the bacteriophage as an active ingredient.

[0042] The antibiotic of the present invention comprises a preservative, a bactericide, and an antibacterial agent. The antibiotic of the present invention can be used to prevent, treat, alleviate symptoms, and suppress various diseases caused by Salmonella enterica.

[0043] The antibiotic including the bacteriophage of the present invention has the advantage of having a very high specificity for Salmonella enterica compared to conventional antibiotics, and thus can selectively eliminate only the pathogenic Salmonella enterica without killing beneficial bacteria, making it highly valuable as an antibiotic with no side effects.

[0044] When the bacteriophage of the present invention is used as an antibiotic, unlike conventional antibiotics, it does not induce resistance or tolerance in pathogens, so it can be used as a novel antibiotic with a longer product life cycle than conventional antibiotics.

[0045] That is, the antibiotic containing the bacteriophage of the present invention as an active ingredient can fundamentally solve the problem of resistance and extend the product life cycle as an antibiotic.

[0046] In addition, the present invention provides livestock feed or drinking water containing the bacteriophage as an active ingredient.

[0047] Livestock use more antibiotics than humans, and the use of antibiotics as feed additives in livestock and fisheries accounts for 54% of total antibiotic sales. In particular, preventative antibiotic administration increases the risk of developing resistant bacteria, and antibiotic residues in livestock can be transmitted to humans. The antibiotic of the present invention can be used as an antibiotic for feed additives.

[0048] The feed additive of the present invention may be in the form of a dry or liquid formulation, and may also include one or more enzyme formulations. The added enzyme preparation can be in either dry or liquid state, and the enzyme preparation includes a fat-decomposing enzyme such as lipase, phytase that breaks down phytic acid to create phosphate and inositol phosphate, amylase that hydrolyzes the α-1,4-glycoside bond contained in starch and glycogen, phosphatase that hydrolyzes organic phosphate esters, carboxymethylcellulase that breaks down cellulose, xylanase that breaks down xylose, maltase that hydrolyzes maltose into two molecules of glucose, and saccharose that hydrolyzes the glucose-fructose mixture. It can be selected and used from the group consisting of sugar-producing enzymes such as invertase, etc.

[0049] The feed additive containing the bacteriophage of the present invention may further include other non-pathogenic microorganisms. Microorganisms that may be added include, but are not limited to, Bacillus subtilis, which can produce protein-decomposing enzymes, lipolytic enzymes, and sugar-converting enzymes; Lactobacillus sp., which has physiological activity and organic matter-decomposing ability under anaerobic conditions such as the stomach of a cow; filamentous fungi, such as Aspergillus oryzae, which have the effect of increasing the weight of livestock, increasing milk production, and increasing the digestibility and absorption rate of feed; and yeasts, such as Saccharomyces cerevisiae.

[0050] Feed raw materials such as peanuts, peas, sugar beets, pulp, grain by-products, animal viscera meal, and fish meal, as well as various grains and soybean proteins, can be used unprocessed or processed.

[0051] In addition, the present invention provides a disinfectant or detergent containing the bacteriophage as an active ingredient.

[0052] The disinfectant containing the bacteriophage of the present invention as an active ingredient has high utility in food hygiene, especially in the prevention of food poisoning. It can be used as a disinfectant and food additive to prevent Salmonella contamination in the food industry, and can be utilized in the livestock industry. Furthermore, it can be used for spraying to remove Salmonella bacteria in effluent from sewage treatment plants, and it can also be useful as a disinfectant for cooking areas and equipment, sanitary facility equipment, medical facility equipment, public facilities such as daycare centers, and toys.

[0053] The present invention provides a novel bacteriophage having a specific killing ability against Salmonella enterica and an antimicrobial composition comprising the same, and a composition containing the bacteriophage as an active ingredient can be usefully used as a composition for preventing or treating infectious diseases caused by Salmonella enterica bacteria, livestock feed, drinking water, detergents, and disinfectants.

[0054] Figure 1 is a diagram showing the results of isolating a bacteriophage of the present invention having a specific killing ability against Salmonella enterica.

[0055] Figure 2 is a diagram showing the results of analyzing the genomic DNA of the bacteriophage of the present invention by electrophoresis.

[0056] Hereinafter, the present invention will be described in more detail through the following examples and experimental examples. However, the scope of the present invention is not limited to the following examples and experimental examples, but includes modifications of technical concepts equivalent thereto.

[0057] Example 1. Isolation of a bacteriophage capable of killing Salmonella enterica bacteria.

[0058] Stool was collected from infants and toddlers, suspended in PBS, centrifuged, and the supernatant was collected, filter-sterilized, and stored at 4°C. Salmonella enterica was cultured overnight in LB broth, and the filtered phage was enriched 5-fold using LB broth for 4 hours.

[0059] Afterwards, the supernatant was collected by centrifugation, sterilized by filtering, and stored at 4°C. Phage isolation was performed by repeating the soft agar overlay method (Double-layer agar (DLA) method) three times.

[0060] As a result, a phage targeting Salmonella enterica was isolated from infant and toddler stool samples (Fig. 1).

[0061] The present inventors selected a bacteriophage capable of specifically killing Salmonella enterica, and deposited the isolated bacteriophage with the Biological Resource Center of the Korea Research Institute of Bioscience and Biotechnology on August 18, 2023, under the accession number KCTC 15560BP.

[0062] Example 2. Identification of bacteriophages

[0063] To analyze the DNA pattern of bacteriophage, the genomic DNA of bacteriophage was extracted, cut with restriction enzymes, and then analyzed by electrophoresis.

[0064] More specifically, a genomic DNA extraction experiment was performed on a bacteriophage having a specific killing ability against E. coli isolated using the soft agar overlay method (Double-layer agar (DLA) method) and a bacteriophage having a specific killing ability against Salmonella enterica of the present invention.

[0065] A phage sample was prepared by suspending the corresponding phage plaque in PBS, adding RNase A and DNase I, and incubating at 37°C for 1 hour. Afterwards, 0.5 M EDTA solution was added, gently mixed, and incubated at 65°C for 30 minutes. Proteinase K was added, incubated at 37°C for 20 minutes, and SDS was added to a final concentration of 5%.

[0066] The above mixture was incubated at 50°C for 1 hour, 1 volume of PCI was added, vortexed, and centrifuged to collect the supernatant. DNA was precipitated using 100% ethanol, and the DMA pellet was washed using 80% ethanol. After that, DNA samples were prepared using DW, and the ladder and the two types of DNA samples were electrophoresed on a 0.7% agarose gel.

[0067] As a result, the genomic DNA extraction of a bacteriophage with specific killing ability against Salmonella enterica was confirmed (Fig. 2).

[0068] Example 3. Evaluation of pH stability of bacteriophage

[0069] To determine whether the bacteriophage selected and isolated in Example 1 can be stable at low pH in the chicken stomach, its stability was evaluated over a variety of pH ranges (pH 2 to 11).

[0070] Sodium acetate buffer (pH 2.1, 4.0, 5.5, and 6.4), sodium citrate buffer (pH 2.5, 3.0, and 3.5), sodium phosphate buffer (pH 6.9 and 7.4), and Tris solution (Tris-HCl, pH 8.2, 9.0, 9.8, and 11.0) were prepared at 0.1 M each at various pH solutions.

[0071] 190 μL of pH solution and 1.1 x 10 1110 μL of bacteriophage solutions with a titer of pfu / mL were mixed to make the concentration of each pH solution 1 M, and then left to stand at room temperature for 2 hours. These were serially diluted, and 10 μL of each serial dilution was dropped according to the soft agar overlay method, and then cultured at 37°C for 18 hours, and the titer was measured by the presence or absence of lysis.

[0072] Relative stability was confirmed by comparing the change in titer according to pH change based on the titer of the bacteriophage at 0 hours.

[0073] As a result, it was confirmed that the bacteriophage of the present invention is very stable without losing activity at pH 3 to 11.

[0074] Example 4. Evaluation of temperature-dependent stability of bacteriophages

[0075] The following experiment was conducted to confirm the stability against heat generated during the formulation process when using bacteriophage as a feed additive.

[0076] 1.0 x 10 11 200 μL of bacteriophage solution with a titer of pfu / mL was incubated at 37, 45, 55, 60, 70, and 80°C for 0, 10, 30, 60, and 120 minutes, respectively. The treated experimental culture solution was serially diluted, and 10 μL of each dilution was dropped according to the soft agar overlay method, and the solution was cultured at 37°C for 18 hours, and the titer was measured by lysis. The relative stability according to temperature and exposure time was compared based on the titer at 0 minute and 37°C.

[0077] As a result, it was confirmed that the bacteriophage of the present invention did not lose activity even when exposed to 70°C for 2 hours.

[0078] Example 5. Evaluation of Salmonella enterica growth inhibition by bacteriophage.

[0079] To evaluate the growth inhibition effect of the isolated bacteriophage on Salmonella enterica, we investigated whether it had specific killing ability.

[0080] The Salmonella enterica bacteria used in the killing activity test were 10 species in total, which were isolated and identified as Salmonella enterica bacteria by the present inventors. The bacteriophage of the present invention had killing activity against 9 species of the Salmonella enterica bacteria that were the subject of the test. Meanwhile, killing activity against Haemophilus parasuis, Enterococcus faecalis, Streptococcus uberis, and Pseudomonas aeruginosa was also tested, but the bacteriophage of the present invention did not have killing activity against these bacteria.

[0081] Through this, it is suggested that the bacteriophage of the present invention has a specific killing ability against Salmonella enterica bacteria and can exert an antibacterial effect against a large number of Salmonella enterica bacteria. This indicates that the bacteriophage of the present invention can be utilized as an effective ingredient of a composition for the purpose of preventing and treating Salmonella enterica infection.

[0082] Example 6. Prevention of Salmonella enterica infection by bacteriophage.

[0083] 1 x 10 in one tube containing 9 mL of TSB medium 11 100 μL of bacteriophage solution at the pfu / mL level was added, and the same amount of TSB medium was added to another tube containing 9 mL of TSB medium.

[0084] Next, a culture medium of Salmonella enterica was added to each tube so that the absorbance at 600 nm was 0.5. After adding Salmonella enterica, the tubes were transferred to an incubator at 37°C and cultured while observing the growth status of Salmonella enterica.

[0085] As a result, inhibition of Salmonella enterica growth was observed in the tube to which the bacteriophage solution was added, whereas no inhibition of Salmonella enterica growth was observed in the tube to which the bacteriophage solution was not added (Table 1).

[0086] Inhibition of growth of Salmonella enterica OD 600 Absorbance valueIncubation 0 minIncubation 60 minAfter incubation 90 minWithout bacteriophage added0.50.81.1With bacteriophage added0.50.30.1

[0087] Through this, it can be confirmed that the bacteriophage of the present invention has the ability to not only inhibit the growth of Salmonella enterica bacteria but also kill them, suggesting that the bacteriophage of the present invention can be utilized as an effective ingredient of a composition for the purpose of preventing infection with Salmonella enterica bacteria.

[0088] Example 7. Treatment of Salmonella enterica infection using bacteriophage.

[0089] The therapeutic effect of bacteriophages on animals infected with Salmonella enterica was evaluated.

[0090] Three groups of chickens were prepared, each group containing 20 chickens. Group 1 was the control group and was not infected with Salmonella enterica, and group 2 was infected with 1 x 10 9 Infection was achieved by oral administration of Salmonella enterica at 1 x 10 CFU, and group 3 received 1 x 10 9 Infection was achieved by oral administration of Salmonella enterica 10 CFU per kg of feed and bacteriophage solution was administered at a dose of 10 9 The mixture was administered at a concentration of 10 PFU for 30 days. Afterwards, the survival rate of the chickens was tracked for 30 days.

[0091] As a result, it was confirmed that the death of chickens began 14 days after infection, and after 30 days, group 2 showed a survival rate of 35%, while group 3 showed a survival rate of 75%.

[0092] Through this, it was confirmed that the survival rate of chickens administered the bacteriophage of the present invention was significantly higher than that of chickens not administered, and it was shown that the bacteriophage of the present invention has an effect of treating (curing) a disease caused by Salmonella enterica when used as a feed additive.

[0093] Although the embodiments of the present invention have been described above, those skilled in the art will understand that the present invention can be implemented in other specific forms without altering the technical spirit or essential characteristics of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not limiting.

[0094] [Accession number]

[0095] Name of depositor: Korea Research Institute of Bioscience and Biotechnology

[0096] Accession number: KCTC15560BP

[0097] Date of acceptance: 20230818

[0098]

Claims

1. A bacteriophage having the ability to specifically kill Salmonella enterica bacteria and deposited under the accession number KCTC 15560BP.

2. In paragraph 1, A bacteriophage characterized in that the bacteriophage has acid resistance in the range of pH 3 to 11.

3. In paragraph 1, A bacteriophage characterized in that the above bacteriophage has heat resistance in the range of 37 to 70°C.

4. A composition for preventing or treating an infectious disease caused by Salmonella enterica, comprising the bacteriophage of paragraph 1 as an active ingredient.

5. In paragraph 4, A composition characterized in that the infectious disease caused by the above Salmonella enterica bacteria is salmonellosis or salmonella food poisoning.

6. A method for preventing or treating an infectious disease caused by Salmonella enterica, comprising a step of administering a composition containing the bacteriophage of paragraph 4 as an active ingredient to a subject other than a human.

7. In paragraph 6, A method characterized in that the infectious disease caused by the above Salmonella enterica bacteria is salmonellosis or salmonella food poisoning.

8. An antibiotic containing the bacteriophage of paragraph 1 as an active ingredient.

9. Livestock feed or drinking water containing the bacteriophage of paragraph 1 as an active ingredient.

10. A disinfectant or detergent containing the bacteriophage of paragraph 1 as an active ingredient.

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