Riemerella anatipestifer bacteriophage and its application

Abstract

The present invention belongs to the field of microbial technology and relates to a Riemerella anatipestifer phage and its application. The Riemerella anatipestifer phage provided by the present invention is RA-XHX1, which is preserved in the China Center for Type Culture Collection with a preservation number of CCTCC NO: M 20241268 and is classified and named as Riemerella anatipestifer phage (Riemerella anatipestifer bacteriophage ). The bacteriophage is double-stranded DNA, Myoviridae, and can form clear plaques on solid culture medium, with no halo around and clear and regular edges; the bacteriophage has a good disinfecting effect on Riemerella anatipestifer in the space environment, especially the highly pathogenic Riemerella anatipestifer, and can be used in the preparation of drugs for the prevention and treatment of Riemerella anatipestifer infection to achieve a broad-spectrum antibacterial effect.

Description

Technical Field

[0001] The invention belongs to the technical field of microorganisms and relates to a Riemerella anatipestifer bacteriophage and application thereof. Background Art

[0002] Riemerella anatipestifer (Riemerella anatipestifer , RA), also known as duck pasteurella disease, duck infectious serositis, duck septicemia, and duck plague syndrome, belongs to the Flavobacteriaceae family. It is a pathogen that causes infectious serositis in ducklings aged 1 to 8 weeks, especially 2 to 3 weeks old. It is one of the bacterial infectious diseases that cause duck farming industry.

[0003] Riemerella anatipestifer is a contact, bacterial infectious disease that is distributed in an epidemic manner in my country without obvious seasonality. The disease was first discovered in the United States. The first Riemerella anatipestifer disease in my country occurred in Beijing. Since then, the disease has occurred throughout the country, especially in areas with dense duck farming. The source of infection of Riemerella anatipestifer disease is mainly ducks, geese and other animals infected with Riemerella anatipestifer. In addition, RA can also harm goslings, pheasants, turkeys and other animals. Riemerella anatipestifer mainly enters the body of ducks and other animals through wounds or other routes such as air, contaminated feed and drinking water to reproduce, and reaches the organs of the body through blood circulation, causing inflammation in various organs in the body including the brain, and typical symptoms of air sacitis, pericarditis and meningitis appear.

[0004] At present, the commonly used drugs for the treatment of Riemerella anatipestifer include antibiotics and antibacterial Chinese medicine. Antibiotics include florfenicol, kanamycin, enrofloxacin, gentamicin, streptomycin sulfate, oxytetracycline, chloramphenicol, etc.; antibacterial Chinese medicines commonly used are rhubarb, coptis root, isatis root, dandelion, pomegranate peel, etc. However, due to the long-term use of drugs, Riemerella anatipestifer is very easy to develop drug resistance, which leads to the gradual weakening of the efficacy of drugs in the process of preventing and treating duck plague caused by Riemerella anatipestifer, and the continuous increase of capital investment during treatment.

[0005] Bacteriophage, also known as bacterial virus, is a microorganism that completes proliferation in bacteria and releases itself into the environment by invading and lysing bacteria. It can infect a variety of bacteria, has strict host specificity, and has obvious advantages in the field of treating host bacterial infections. At present, a large number of studies have shown that phage therapy does not produce obvious side effects, and the safety of phage therapy has been preliminarily recognized. Faced with the increasingly serious problem of antimicrobial resistance, phages can provide a new treatment direction. For example, phage cocktail therapy based on a mixture of multiple phages can accurately and efficiently eliminate host bacteria and achieve good results in the treatment of bacterial infections; and the method of modifying the receptor binding protein and lytic enzyme of phage can expand the host spectrum of phages. Therefore, it is urgent to develop a phage preparation that can both prevent and treat, has significant effects and is safe to use, in order to meet the challenge of Riemerella anatipestifer. Summary of the invention

[0006] In view of the shortcomings of the prior art, the object of the present invention is to provide a Riemerella anatipestifer phage and its application. The present invention provides a phage RA-XHX1 capable of lysing Riemerella anatipestifer, which has a wide lysis spectrum and can lyse clinical strains of Riemerella anatipestifer isolated from the environment or the feces of diseased ducks. It can be used alone or in combination with other substances, and can provide a safe, non-toxic, and non-resistant phage disinfection product for disinfecting and purifying the environment.

[0007] To achieve this object, the present invention adopts the following technical solutions:

[0008] The present invention provides a Riemerella anatipestifer phage RA-XHX1, which is isolated from sewage from a duck farm in Heze City, Shandong Province, and has been deposited in the China Center for Type Culture Collection on June 17, 2024. The depository address is Wuhan University, China, zip code 430072, and the deposit number is CCTCC NO: M 20241268. The classification name is Riemerella anatipestifer phage (Riemerella anatipestifer bacteriophage ).

[0009] The invention discloses a Riemerella anatipestifer phage RA-XHX1 with a deposit number of M 20241268. The phage can form a transparent plaque on a 1.2% LB agar medium, with no halo around it and clear and regular edges. The enzyme digestion map of its genomic nucleic acid shows that the phage nucleic acid is double-stranded DNA (dsDNA). According to the "Taxonomy of Viruses - Eighth Report of the International Committee on Taxonomy of Viruses" published by the International Committee on Taxonomy of Viruses (ICTV) in 2005, the phage belongs to the family Myoviridae ( Myoviridae ). The phage can maintain high activity at 30-50°C and can exist stably at pH 4.0-10.0.

[0010] The optimal infection multiplicity (MOI) of the Riemerella anatipestifer phage RA-XHX1 provided by the present invention is 0.001. Under this condition, the phage RA-XHX1 can replicate to 3×10 9 PFU / mL, indicating that this bacteriophage RA-XHX1 has a strong replication ability. Moreover, the incubation period of bacteriophage RA-XHX1 infecting the host bacteria is about 10 minutes, the duration of the outbreak is about 50 minutes, and the average outbreak volume is 56, which has a high lytic activity.

[0011] The present invention provides a phage composition, comprising the Riemerella anatipestifer phage RA-XHX1 as described above.

[0012] The present invention also provides use of the Riemerella anatipestifer phage RA-XHX1 or the phage composition described above in preparing a drug for preventing or treating a disease caused by Riemerella anatipestifer infection.

[0013] The term "prevention" herein refers to all actions including suppressing or delaying the disease by administering the bacteriophage; the term "treatment" herein refers to all actions including making the disease better or improving by administering the bacteriophage.

[0014] The above-mentioned drugs can be used to prevent or treat infection by Riemerella anatipestifer in humans and animals (chickens, pigs, cattle, geese, ducks, turkeys, etc.).

[0015] Furthermore, the present invention provides a phage pharmaceutical preparation, wherein the active ingredient of the phage pharmaceutical preparation includes the Riemerella anatipestifer phage RA-XHX1 as described above or the phage composition as described above.

[0016] Furthermore, the potency of Riemerella anatipestifer phage RA-XHX1 in the phage pharmaceutical preparation is preferably ≥1×10 10 PFU / mL.

[0017] Furthermore, the bacteriophage pharmaceutical preparation further comprises a pharmaceutically acceptable carrier; the dosage form of the bacteriophage pharmaceutical preparation comprises one or more of a solution, a powder, a gel, a granule, an emulsion, a suspension and a lyophilized agent.

[0018] As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier or diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered active ingredient.

[0019] Moreover, the present invention also provides a feed additive, which comprises the Riemerella anatipestifer phage RA-XHX1 or the phage composition as described above. The feed additive is mixed with feed and then fed to achieve the effect of preventing or treating Riemerella anatipestifer infection.

[0020] In addition, the present invention also provides a disinfectant, which comprises the Riemerella anatipestifer phage RA-XHX1 as described above or the phage composition as described above. The concentration of Riemerella anatipestifer phage RA-XHX1 in the disinfectant is preferably ≥1×10 7 PFU / mL.

[0021] Furthermore, the disinfectant may also contain other active ingredients or other auxiliary agents for inhibiting or eliminating bacteria in the environment, such as auxiliary agents that can prolong the duration of bacteriophages.

[0022] Secondly, the present invention also provides the use of the above-mentioned disinfectant, which disinfects the breeding environment, feed, drinking water or the body surface of poultry and livestock against Riemerella anatipestifer by spraying or immersing.

[0023] The farm environment refers to the breeding equipment, ground, walls, feces, bedding and other spatial environments.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] Riemerella anatipestifer RA is mainly transmitted through the digestive tract, respiratory tract and other modes, and secondly, it can also be infected through skin damage, which seriously affects the breeding of waterfowl, especially the impact on the dense duck breeding areas is more serious. The long-term use of drugs makes Riemerella anatipestifer very easy to develop drug resistance, which not only leads to the continuous increase in the cost of the treatment period, but also significantly weakens the efficacy of the drugs. The present invention discovers and isolates a Riemerella anatipestifer phage RA-XHX1, which has a strong Riemerella anatipestifer killing activity and a wide lysis spectrum, can specifically lyse Riemerella anatipestifer, is used in the preparation of drugs for preventing and treating Riemerella anatipestifer infection, or as a feed additive for feeding, or made into a disinfectant to disinfect the breeding environment, feed, drinking water or body surface of ducks to kill Riemerella anatipestifer, and can achieve a broad-spectrum bactericidal effect. This method is completely safe for poultry and can be used as an ideal alternative to antibiotics and vaccines. It has no residue, will not cause drug resistance, and is very environmentally friendly. It has shown very good clinical application prospects in the prevention and treatment of Riemerella anatipestifer infection, and has found a new and effective treatment option for Riemerella anatipestifer infection, effectively solving the problem of drug resistance of Riemerella anatipestifer.

[0026] The Riemerella anatipestifer phage RA-XHX1 provided by the present invention can not only maintain high activity at 30-50°C and stably exist in an environment with a pH of 4.0-10.0; and its optimal multiplicity of infection (MOI) is 0.001. Under this condition, the phage RA-XHX1 can replicate to 3×10 9 PFU / mL or above, with strong replication ability; and, the incubation period of bacteriophage RA-XHX1 infecting host bacteria is about 10 minutes, the outbreak duration is about 50 minutes, the average outbreak volume is 56, and it has high lytic activity.

[0027] Description of biological deposit:

[0028] A Riemerella anatipestifer bacteriophage RA-XHX1 was deposited in the China Center for Type Culture Collection on June 17, 2024. The deposit address of the deposit unit is Wuhan University, China, Postal Code 430072, the deposit number is CCTCC NO: M 20241268, and the classification name is Riemerella anatipestifer bacteriophage RA-XHX1. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is a plaque image of the Riemerella anatipestifer phage RA-XHX1 purified in Example 2 of the present invention on a plate;

[0030] Figure 2 This is a temperature tolerance diagram of the Riemerella anatipestifer bacteriophage RA-XHX1 of the present invention;

[0031] Figure 3 This is a pH tolerance diagram of the Riemerella anatipestifer bacteriophage RA-XHX1 of the present invention;

[0032] Figure 4 The optimal infection multiplicity diagram of the Riemerella anatipestifer bacteriophage RA-XHX1 of the present invention;

[0033] Figure 5 The figure is a one-step growth curve of the Riemerella anatipestifer phage RA-XHX1 of the present invention in LB culture medium at 37°C. DETAILED DESCRIPTION

[0034] The technical solution of the present invention is described in detail below in conjunction with specific embodiments and their accompanying drawings. The embodiments recorded herein are specific embodiments of the present invention, which are used to illustrate the concept of the present invention; these descriptions are explanatory and exemplary and should not be construed as limitations on the embodiments of the present invention and the scope of protection of the present invention. In addition to the embodiments recorded herein, those skilled in the art can also adopt other obvious technical solutions based on the contents disclosed in the claims of this application and its specification, including technical solutions that adopt any obvious replacements and modifications to the embodiments recorded herein.

[0035] Unless otherwise specified, the reagents and equipment involved in the following examples were purchased from commercial channels. Strains, reagents and culture media involved in the examples:

[0036] The host bacteria involved in the embodiment is Riemerella anatipestifer, which is isolated from the feces of sick ducks in a duck farm and preserved by Shandong New Route Biotechnology Co., Ltd.

[0037] 1.2% LB agar medium / plate (200 mL): weigh 2 g of tryptone, 2 g of sodium chloride, 1 g of yeast powder and 2.4 g of agar in 200 mL of distilled water, heat and boil until completely dissolved, autoclave at 121°C for 15 min, and cool for later use.

[0038] 0.6% LB agar medium / plate (200 mL): weigh 2 g of tryptone, 2 g of sodium chloride, 1 g of yeast powder and 1.2 g of agar in 200 mL of distilled water, heat and boil until completely dissolved, sterilize at 121°C for 15 min, and cool for later use.

[0039] LB liquid medium (200 mL): weigh 2 g of tryptone, 2 g of sodium chloride, and 1 g of yeast powder in 200 mL of distilled water, heat and boil until completely dissolved, sterilize at 121°C for 15 min, and cool for later use.

[0040] SM solution (1L): Weigh 6.055g of tris(hydroxymethyl)aminomethane (Tris) and dissolve it in 20mL of distilled water. Use concentrated hydrochloric acid to adjust the pH to 7.5 and make up to 50mL. Then add 5.8g of NaCl and 2g of MgSO4, and make up to 1L after dissolution. Sterilize at 121℃ for 15min and cool for later use.

[0041] 1.2% TSB agar medium / plate (200 mL): weigh 2 g of tryptone, 2 g of sodium chloride, 1 g of yeast powder and 2.4 g of agar in 200 mL of distilled water, heat and boil until completely dissolved, autoclave at 121°C for 15 min, and cool for later use.

[0042] Example 1 Phage Isolation and Preparation

[0043] The host bacteria Riemerella anatipestifer was streaked on 1.2% LB agar medium. After culturing overnight, a single colony was picked and inoculated into 1 ml LB liquid culture medium. After shaking culture at 37°C for 5-6 h, it was used as the host bacteria culture for later use.

[0044] On January 15, 2024, sewage was collected from a duck farm in Heze City, Shandong Province. The sewage supernatant was filtered through a double-layer filter paper, centrifuged at 10,000 rpm for 20 minutes, and then the sewage supernatant was filtered with a 0.22 μm filter membrane; 10 mL of the filtered supernatant was added, 0.5 mL of the overnight host bacteria culture was added, and then sterile CaCl2 mother solution was added to a final concentration of 1.25 mM, mixed, and then 20 ml of LB liquid culture medium was added, and the mixture was allowed to react at room temperature for 30 minutes, and then placed at 37°C for 6 to 8 hours to obtain the culture; then the culture was centrifuged at 12,000 rpm, 4°C for 30 minutes, and the supernatant was taken; 10 mL of this supernatant was taken, 0.5 mL of the overnight host bacteria culture was added again, and sterile CaCl2 mother solution was added to a final concentration of 1.25 mM, mixed, and then 20 ml LB liquid culture medium was cultured and centrifuged according to the above culture method to obtain enriched supernatant; enriched again according to the above test method, and the supernatant enriched three times was filtered with a 0.22 μm filter membrane to form a phage stock solution.

[0045] Divide the 1.2% LB agar plate into two areas: take 0.1mL of the host bacterial culture and drop it in the center of the plate, and spread the bacterial solution evenly with a spreader; after it is dried, take 10uL of the phage stock solution and drop it in one of the areas; after it is naturally dried, place it in a 37℃ incubator for 10 hours, and observe whether there are plaques formed in the phage drop area. If there are plaques, it proves that phages exist.

[0046] Take 0.1 mL of the phage stock solution and make a series of 10-fold dilutions. -2 , 10 -4 and 10 -6 0.1 mL of each diluent was mixed with 0.1 mL of host bacterial culture, and after 15 min at room temperature, about 4 mL of melted 0.6% LB agar medium was added, and after mixing, it was quickly poured into the upper layer of 1.2% LB agar medium plate, shaken and left flat for 10 min to solidify, and placed in a 37°C incubator for 12 h and observed to obtain a double-layer plate with a single plaque.

[0047] Example 2 Amplification and purification of bacteriophage RA-XHX1

[0048] On the double-layer plate formed with a single plaque obtained in Example 1, a single plaque with a larger diameter was picked up with the tip of a pipette, inoculated into 3-5 ml LB liquid culture medium, 0.1 mL of phage host bacterial solution was added, mixed, allowed to act at room temperature for 15 min, cultured at 37°C for 10-14 h, centrifuged at 12000 rpm, 4°C for 10 min, the supernatant was taken, and 0.3% chloroform was added; the double-layer experiment was repeated, and single plaques were picked up repeatedly 4-5 times, and the phage was purified into plaques of the same size to obtain a phage culture.

[0049] Take 1 mL of the host bacteria culture cultured in Example 1, add 0.3 mL of phage culture, and incubate at 37°C for 20 min to allow the phage particles to adsorb to the host bacteria; add 100 mL of LB liquid culture medium, and then add CaCl2 mother solution to a final concentration of 1.25 mM, shake culture at 37°C for 12 to 16 h, centrifuge at 12000 rpm, 4°C for 10 min, and take the supernatant, which is the phage lysate.

[0050] The double-layer plate method was used to detect the phage titer: the purified phage lysate was diluted 10 times in a gradient, 0.1 mL of the corresponding phage dilution was taken and mixed with 0.1 mL of the phage host bacterial solution, and then spread on a double-layer agar plate. The plate was incubated at 37°C for about 10 hours, and the plaques on the agar plate were counted. The plate with about 100-200 plaques was selected, and the initial phage concentration calculated according to the dilution multiple was the phage titer. Figure 1 As shown, the phage can form clear plaques in 1.2% LB agar medium, with no halo around, clear and regular edges, and a diameter of 1-2 mm.

[0051] The isolated and purified Riemerella anatipestifer phage was deposited in the China Center for Type Culture Collection on June 17, 2024. The depository address is Wuhan University, China, zip code 430072, and the deposit number is CCTCC NO: M20241268. It is classified and named Riemerella anatipestifer phage ( Riemerella anatipestifer Bacteriophage ).

[0052] Example 3 Experiment on temperature and acid-base tolerance of Riemerella anatipestifer phage RA-XHX1

[0053] Take 1 mL of the purified phage obtained in Example 2 and incubate in a water bath at 30°C, 50°C, 70°C, and 90°C for 30 min and 60 min, respectively. After cooling the sample, measure its titer. Take equal amounts of peptone with a pH value of 2.0 to 13.0, water, and purified phage, respectively, mix them, and measure their titer after incubating in a water bath at 37°C for 2 h.

[0054] Temperature test results such as Figure 2 As shown, the activity of Riemerella anatipestifer phage RA-XHX1 did not change significantly after being exposed to 32-55°C for 30 min and 60 min, respectively; but it decreased rapidly after 50°C, and there was basically no phage after 70°C.

[0055] The pH test results are as follows Figure 3 As shown, the titer of Riemerella anatipestifer phage RA-XHX1 was relatively stable when the pH value was between 4 and 10, but pH values ​​<4 and >10 would cause a significant decrease in the titer, and when the pH value was ≤3 or ≥11, no plaques could be detected.

[0056] Example 4 Host spectrum analysis of Riemerella anatipestifer phage RA-XHX1

[0057] The titer of Riemerella anatipestifer phage RA-XHX1 obtained in Example 2 was adjusted to 1×10 10 PFU / mL is reserved.

[0058] The host spectrum analysis of Riemerella anatipestifer phage RA-XHX1 was performed, and the results are shown in Table 1:

[0059] Table 1 Host spectrum analysis of Riemerella anatipestifer phage RA-XHX1

[0060]

[0061] Note: “-” indicates no lysis; “+” indicates lysis with clear lysis spots.

[0062] As can be seen from Table 1, the Riemerella anatipestifer phage RA-XHX1 has a lytic effect on all five strains of Riemerella anatipestifer.

[0063] Example 4 Optimal multiplicity of infection of Riemerella anatipestifer phage RA-XHX1

[0064] 1 ml of phage lysate was added according to the multiplicity of infection ( Multiplicity of Infection, The MOI was 0.0001, 0.001, 0.01, 0.1, and 1, and was added to the phage host bacterial solution (1.0×10 8 CFU / mL) and cultured at 37 °C and 180 r / min for 5 h. The titer of phage in phage lysate was determined by double-layer plate method, and the multiplicity of infection that produced the highest titer was the optimal MOI.

[0065] like Figure 4 As shown in the figure, the optimal infection multiplicity (MOI) of Riemerella anatipestifer phage RA-XHX1 is 0.001. Under this condition, Riemerella anatipestifer phage RA-XHX1 can replicate to 3×10 9PFU / mL or above, indicating that Riemerella anatipestifer phage RA-XHX1 has a strong replication ability.

[0066] Example 5 One-step growth curve of bacteriophage RA-XHX1

[0067] Take the suspension of Riemerella anatipestifer in the logarithmic growth period, inoculate Riemerella anatipestifer RA-XHX-1-1 and bacteriophage RA-XHX1 according to the optimal infection multiplicity ratio, water bath at 37°C for 10 min, then centrifuge at 12000 r / min at room temperature for 5 min, discard the supernatant, remove the free phage not adsorbed on the host, and wash twice with TSB broth medium. Resuspend the precipitate in TSB broth medium at 37°C, quickly place it in a shaking incubator at 37°C and 200 r / min for shaking culture and timing. Sample and count every 10 minutes within 60 minutes, draw a growth curve with time as the horizontal axis and the logarithm of the phage titer as the vertical axis, obtain the incubation period and lysis period of the phage, and calculate the average lysis amount.

[0068] The formula for calculating the average lysis amount is: average lysis amount = phage titer at the end of the outbreak / host bacteria concentration at the beginning of infection.

[0069] The results are as follows Figure 5 As shown, the incubation period of Riemerella anatipestifer phage RA-XHX1 infecting the host bacteria is about 10 minutes, the outbreak duration is about 45 minutes, the average outbreak volume is 156, and it has a high lytic activity.

[0070] Example 6 Animal protection test of bacteriophage against Riemerella anatipestifer in ducklings

[0071] Experimental procedures: (1) Sixty 6-day-old ducklings were randomly divided into an oral test group and a control group, with 30 ducks in each group. The oral test group and the control group were intraperitoneally injected with RA-XHX-1-1 (serotype 1) Riemerella anatipestifer, with each duck injected with 0.5 ml (1×10 6 CFU / ml), 6 hours after the challenge, the oral test group was given oral phage RA-XHX1 every day, 0.5 ml (1×10 6PFU / ml), and the drug was used continuously for 3 days; the control group was given the same dose of normal saline, and after the drug was used, it was observed for 7 consecutive days, and the death of ducklings was recorded. The results showed that 10% of the ducklings in the control group survived, and more than 90% of the ducklings in the oral test group survived after oral administration of bacteriophage RA-XHX1. This shows that bacteriophage RA-XHX1 is effective in treating duckling serositis caused by Riemerella anatipestifer after oral administration, and can better protect ducklings from the attack of Riemerella anatipestifer, providing a new possibility for the development of bacteriophage preparations that can both prevent and treat, have significant effects and are safe to use in response to the challenge of Riemerella anatipestifer.

[0072] The applicant declares that the above is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention shall fall within the protection scope and disclosure scope of the present invention.

Claims

1. A Riemerella anatipestifer phage, characterized in that: The Riemerella anatipestifer phage is RA-XHX1, which is deposited in the China Center for Type Culture Collection with a deposit number of CCTCC NO: M 20241268 and is classified as Riemerella anatipestifer phage (Riemerella anatipestifer bacteriophage ).

2. A bacteriophage composition, characterized in that: The invention comprises the Riemerella anatipestifer phage as claimed in claim 1.

3. Use of the Riemerella anatipestifer phage according to claim 1 or the phage composition according to claim 2 in the preparation of a medicament for preventing or treating a disease caused by Riemerella anatipestifer infection.

4. A bacteriophage pharmaceutical preparation, characterized in that: The active ingredient of the bacteriophage pharmaceutical preparation includes the Riemerella anatipestifer bacteriophage according to claim 1 or the bacteriophage composition according to claim 2.

5. The bacteriophage pharmaceutical preparation according to claim 4, characterized in that The bacteriophage drug preparation further comprises a pharmaceutically acceptable carrier; the dosage form of the bacteriophage drug preparation comprises one or more of a solution, a powder, a gel, a granule, an emulsion, a suspension and a lyophilized agent.

6. A feed additive, characterized in that: The feed additive comprises the Riemerella anatipestifer phage according to claim 1 or the phage composition according to claim 2.

7. A disinfectant, characterized in that: The disinfectant comprises the Riemerella anatipestifer phage according to claim 1 or the phage composition according to claim 2.

8. The disinfectant according to claim 7, characterized in that The disinfectant also includes an auxiliary agent.

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