Cracking carcinogenic enterobacter bacteriophage RDP-QEC-24001 and application thereof

Abstract

The invention relates to the technical field of microorganisms. The invention provides a lytic enterobacter cancerogenic bacteriophage RDP-QEC-24001, the lytic enterobacter cancerogenic bacteriophage RDP-QEC-24001 is preserved in the General Microbiological Culture Collection Center of the China Committee for Culture Collection of Microorganisms on September 23, 2024, and the preservation number of the lytic enterobacter cancerogenic bacteriophage RDP-QEC-24001 is CGMCC (China General Microbiological Culture Collection Center) No.46191. The invention further provides a preparation method of the lytic enterobacter cancerogenic bacteriophage RDP-QEC-24001. Based on the same inventive concept, the invention also provides a bacteriophage composition. The invention also provides application of the bacteriophage RDP-QEC-24001 for splitting the carcinogenic enterobacter or the bacteriophage composition in preparation of products for preventing and / or treating livestock and poultry diseases caused by the carcinogenic enterobacter and application of the bacteriophage composition in preparation of products for killing and / or inhibiting the carcinogenic enterobacter. The invention also provides a bacteriophage pharmaceutical preparation, a drinking water additive, a feed additive, a disinfectant or a cleaning agent. The split carcinogenic enterobacteriophage RDP-QEC-24001 provided by the invention is high in titer, good in treatment effect and high in splitting rate.

Description

Technical Field

[0001] The invention relates to the field of biotechnology, and in particular to a phage RDP-QEC-24001 that lyses carcinogenic Enterobacteriaceae and applications thereof. Background Art

[0002] Enterobacter cancerogenus strain belongs to the genus Escherichiacoli and is a Gram-negative, short, thick rod with flagella all over the body, no spores, and facultative anaerobic. It is widely present in water, sewage, soil, and vegetables. It is an intestinal colonizer and can cause pathogenic infections under various conditions, including bone and joint infections associated with severe trauma or crush injuries.

[0003] In addition, it has been shown that carcinogenic Enterobacter has a high level of resistance to antibiotics such as amoxicillin. Because it can produce bioemulsifiers and degrade azo dye pollutants and L-phosphinothricin herbicides, it is mainly used as an insecticide and soil conditioner in practical applications. At the same time, as an intestinal colonizing bacteria, carcinogenic Enterobacter can colonize in large numbers in the intestines of domestic chickens, continuously excrete bacteria into the external environment throughout the entire breeding and slaughtering production process, and eventually spread to humans, posing a threat to human life and health.

[0004] There are cases of wound-related infections of bones and joints following environmental exposure to carcinogenic Enterobacteriaceae.

[0005] Bacteriophage is a virus that targets bacteria, mycoplasma, and chlamydia, and has the characteristics of safety and specificity. First, bacteriophage has strong specificity and only lyses the corresponding host bacteria without destroying the normal flora, so it can be widely used in animals. Secondly, the use of bacteriophage has the advantage of no residue, and it can be naturally excreted from the animal body. Thirdly, bacteriophage will not cause pathogens to develop drug resistance, and is effective against Gram-positive, Gram-negative and multi-drug resistant bacteria.

[0006] Therefore, it is urgent to develop a phage product with high titer, good therapeutic effect and high lysis rate for the prevention and treatment of carcinogenic Enterobacteriaceae. Summary of the invention

[0007] The purpose of the present invention is to provide a lytic carcinogenic Enterobacteriaceae phage RDP-QEC-24001 to replace the application of antibiotics in the prevention and treatment of livestock and poultry breeding, and to solve the problems of rapid disease onset and untimely treatment of livestock and poultry, and ineffective medication due to drug resistance of pathogenic bacteria.

[0008] To solve the above problems, the present invention provides the following technical solutions:

[0009] In the first aspect, the present invention provides a lytic carcinogenic Enterobacteriaceae phage (Enterobactercancerogenus strainphage) RDP-QEC-24001, which was isolated from the chicken liver of a farmer in Shandong Province and was deposited in the General Microbiological Center of the China Microbiological Culture Collection Committee on September 23, 2024. The deposit address is: No. 3, Yard No. 1, Beichen West Road, Chaoyang District, Beijing, and the deposit number is CGMCC No. 46191. The carcinogenic Enterobacter QT-24001 used in the present invention is preserved together with the lytic carcinogenic Enterobacteriaceae phage RDP-QEC-24001 of the present invention.

[0010] Observation by electron microscope: The phage is a polyhedral, three-dimensionally symmetrical head wrapped with nucleic acid. Its size is basically 90nm and the genome length is 180642bp. According to the definition of the International Committee on Taxonomy of Viruses (ICTV), the morphology of the phage conforms to the characteristics of the Myotrophaeidae family and belongs to the Myotrophaeidae family. The titer of the lysing carcinogenic Enterobacteriaceae phage DP-QEC-24001 can reach 10 9 pfu / mL, the phage can be stored for a long time at -80℃, and the titer remains stable. The phage can specifically lyse the carcinogenic Enterobacter QT-24001 isolated in this experiment, and its optimal infection multiplicity is 100:1.

[0011] In a second aspect, based on the same inventive concept, the present invention provides a phage composition, comprising the oncogenic Enterobacteriaceae phage RDP-QEC-24001 as described above.

[0012] In a third aspect, based on the same inventive concept, the present invention provides the use of the above-mentioned oncogenic Enterobacteriaceae phage RDP-QEC-24001 or the above-mentioned phage composition in the preparation of products for preventing and / or treating livestock and poultry diseases caused by oncogenic Enterobacteriaceae.

[0013] In a fourth aspect, based on the same inventive concept, the present invention provides the use of the above-mentioned oncogenic Enterobacteriaceae-lytic phage RDP-QEC-24001 or the above-mentioned phage composition in the preparation of a product for killing and / or inhibiting oncogenic Enterobacteriaceae.

[0014] In a fifth aspect, based on the same inventive concept, the present invention provides a phage pharmaceutical preparation, the active ingredient of which includes the above-mentioned oncogenic Enterobacteriaceae phage RDP-QEC-24001 or the above-mentioned phage composition.

[0015] The phage pharmaceutical preparation as described above, wherein the concentration of the lytic carcinogenic Enterobacteriaceae phage RDP-QEC-24001 is at least 10 9 pfu / mL.

[0016] In a sixth aspect, based on the same inventive concept, the present invention provides a drinking water additive, the active ingredients of which include the above-mentioned carcinogenic Enterobacteriaceae phage RDP-QEC-24001 or the above-mentioned phage composition.

[0017] In a seventh aspect, based on the same inventive concept, the present invention provides a feed additive, the active ingredients of which include the above-mentioned carcinogenic Enterobacteriaceae phage RDP-QEC-24001 or the above-mentioned phage composition.

[0018] In an eighth aspect, based on the same inventive concept, the present invention provides a disinfectant, wherein the active ingredient comprises the above-mentioned oncogenic Enterobacteriaceae phage RDP-QEC-24001 or the above-mentioned phage composition. Preferably, the disinfectant can be used to disinfect the chicken breeding environment from oncogenic Enterobacteriaceae by spraying or soaking.

[0019] In a ninth aspect, based on the same inventive concept, the present invention provides a cleaning agent, the active ingredients of which include the above-mentioned carcinogenic Enterobacteriaceae phage RDP-QEC-24001 or the above-mentioned phage composition.

[0020] Compared with the existing technology, the effects and advantages of the present invention are:

[0021] 1. The phage RDP-QEC-24001 provided by the present invention has a high titer and the titer of the phage can reach up to 10 9 pfu / mL or above, which provides a new source for phage products.

[0022] 2. The lysis rate of the oncogenic Enterobacteriaceae phage RDP-QEC-24001 provided by the present invention is as high as 95.37%, which has a good lysis effect on the host and is suitable for use in the breeding process.

[0023] 3. The oncogenic Enterobacteriaceae phage RDP-QEC-24001 provided by the present invention is safe and highly effective, and can replace the use of antibiotics in the prevention and treatment of livestock and poultry breeding, and can be highly efficient and economical in practical applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The plaque picture of the bacteriophage isolated by the present invention;

[0025] Figure 2 This is an electron microscope image of the bacteriophage RDP-QEC-24001 of the present invention;

[0026] Figure 3 This is a one-step growth curve of the bacteriophage RDP-QEC-24001 of the present invention. DETAILED DESCRIPTION

[0027] The following will combine the contents in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used in this specification includes any and all combinations of one or more of the related listed items.

[0029] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0030] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources. The phage RDP-QEC-24001 that lyses carcinogenic Enterobacteriaceae is hereinafter referred to as "phage RDP-QEC-24001" or "RDP-QEC-24001".

[0031] Example 1 Isolation and identification of pathogenic bacteria and bacteriophages

[0032] (1) Isolation and identification of carcinogenic Enterobacteriaceae:

[0033] The chicken liver used in the present invention was collected from a breeder in Shandong in 2024 as a sample for isolation of pathogens and bacteriophages.

[0034] From chicken liver, streak on CHROMagar colorimetric medium aseptically, culture at 37℃ for 18-24h, pick blue or blue-green colonies with a diameter of about 1-2mm and neat edges; streak on LB medium, culture at 37℃ for 18-24h, pick typical colonies and continue streak purification 3 times, pick single colonies and inoculate in 5mL LB medium, culture at 37℃, 200rpm shaking for 4h, and obtain a uniform turbid bacterial suspension. Through 16sRNA molecular identification, it was determined to be carcinogenic Enterobacter, named QT-24001, and stored in a -80℃ refrigerator.

[0035] (2) Phage isolation and identification:

[0036] Phage enrichment: Take an appropriate amount of chicken liver and add an appropriate amount of physiological saline to grind, centrifuge at 10000rpm for 10 minutes to remove large impurities and most bacteria, and filter with a 0.22μm microporous filter to sterilize. Take 0.1ml of filtrate and 0.1ml of host bacterial suspension and add them to 5ml LB broth, place it in a shaker at 37℃ and culture for 6h. After the culture is completed, take 3-4ml, centrifuge at 10000rpm for 5min, filter with 0.22μm to sterilize, and use the filtrate for later use.

[0037] Phage isolation: Take 0.1 ml of the suspension of Enterobacterium carcinogenes QT-24001 and spread it on a double-layer plate. After cooling, add 0.1 ml of the filtrate of the mixed bacterial suspension. After culturing at 37°C for 6-8 hours, remove the transparent spot and soak it in 1 mL of saline for 10 minutes. Dilute it tenfold to 10 -6 , take 10 -4 , 10 -5 , 10 -6 Add 0.1 mL of bacterial suspension to each of the three dilution gradients, add to 3 mL of 0.4% nutrient agar heated to 45-54°C, spread on two plates, and culture in a 37°C incubator for 4-6 hours for purification. Repeat this step 2-3 times until the plaque size is uniform.

[0038] Thus, a phage strain was obtained and named RDP-QEC-24001. The plaque picture of the phage isolated in this example is shown in FIG. Figure 1 shown.

[0039] Depend on Figure 1 It can be seen that the plaques formed by phage RDP-QEC-24001 on the double plates are 2 mm in diameter and are round and transparent.

[0040] (3) Determination of phage titer

[0041] The purified phage was spread on a double-layer plate, and then a single plaque was taken and added to the LB liquid medium with the host bacterial suspension for proliferation. The proliferation liquid was centrifuged at 10000rpm for 5 minutes and filtered through a 0.22μm filter for sterilization. It was diluted tenfold to 10-6 times, and 0.1mL of the last three dilutions of phage dilutions and 0.1mL of host bacterial suspension were taken and spread on a double-layer plate to determine the phage titer.

[0042] Phage titer (pfu / mL) = number of plaques * dilution factor ÷ 0.1.

[0043] The results showed that the plaques had consistent morphology, size and clarity, and had typical lytic phage characteristics; the titer of the phage could reach up to 109pfu / mL or more.

[0044] (4) Preservation of bacteriophages

[0045] The phage proliferation fluid filtrate was mixed with 60% glycerol at a ratio of 1:1 and stored in a -80°C refrigerator.

[0046] Example 2 Electron microscopic observation of bacteriophage

[0047] 1. Experimental methods

[0048] Take more than 10 5 50 μL of PFU / mL phage sample was dropped on the microporous copper mesh, precipitated for 1 min, and excess liquid was removed with filter paper. 50 μL of 1% phosphotungstic acid (PTA) was added to the copper mesh, stained for 5 min, excess dye was removed with filter paper, and after drying, it was observed and photographed with a transmission electron microscope.

[0049] 2. Experimental results and analysis

[0050] Depend on Figure 2 As shown in the figure, the phage has a polyhedral, three-dimensionally symmetrical head wrapped with nucleic acid under an electron microscope. Its size is basically 90nm with a tail, and the tail is about 110nm long. According to the definition of the International Committee on Taxonomy of Viruses (ICTV), the morphology of this phage conforms to the characteristics of the Myotailed Bacteriophage family and belongs to the Myotailed Bacteriophage family.

[0051] Example 3 Phage genome sequencing

[0052] 1. Experimental methods

[0053] After enrichment culture of a single phage, centrifuge at 8000r for 15 minutes at 4°C, add 10% PEG8000 and 0.5M NaCl and let stand overnight, then add an equal amount of chloroform and mix well. After standing and stratification, centrifuge at 5000r for 10 minutes. After removing the chloroform layer and PEG layer, add restriction endonuclease for digestion, and suspend the phage under gradient density cesium chloride conditions. Later, dialyze with TM buffer 3 times, 30 minutes each time, and send to BGI Biological Sequencing Company for whole genome sequencing.

[0054] 2. Experimental results and analysis

[0055] The results are shown in the sequence listing. The full length of the RDP-QEC-24001 genome is 180642 bp.

[0056] Example 4: Determination of the optimal multiplicity of infection

[0057] 1. Experimental methods

[0058] The phage proliferation solution and the host were added to LB at a multiplicity of infection of 100:1, 10:1, 1:1, 1:10, 1:100, and 1:1000, and the total volume of the culture system was ensured to be the same. After shaking culture at 37°C and 160 rpm for 6 hours, centrifuged at 12000 r / min for 5 minutes at room temperature, and the supernatant was spread on two plates to determine its titer. The results are shown in Table 1.

[0059] 2. Experimental results and analysis

[0060] Table 1 Results of optimal multiplicity of infection

[0061]

[0062] As shown in Table 1, when the multiplicity of infection was 100:1, after 6 h of culture, the proliferation fluid was relatively clear and the titer was the highest, reaching 1.92×10 9 cfu / mL, indicating that the optimal infection multiplicity of the oncogenic Enterobacteriaceae phage RDP-QEC-24001 of the present invention is 100:1.

[0063] Example 5: Phage lysis curve of host

[0064] 1. Experimental methods

[0065] Take the bacterial suspension in the logarithmic growth phase, inoculate the carcinogenic Enterobacter QT-24001 and the bacteriophage RDP-QEC-24001 according to the optimal infection multiplicity ratio, water bath for 10 minutes at 37°C, then centrifuge at 12000r / min for 5 minutes at room temperature, discard the supernatant, remove the free bacteriophage not adsorbed on the host, and wash twice with liquid culture medium. Resuspend the precipitate in 37°C liquid culture medium and quickly place it in a 37°C incubator. Take samples at fixed points to determine their titer, and draw a growth curve with time as the horizontal axis and the logarithm of the phage titer as the vertical axis.

[0066] 2. Experimental results and analysis

[0067] The results are as follows Figure 3 As shown, the latent period and lysis period of the phage can be obtained, and the average lysis amount can be calculated. Average lysis amount = phage titer at the end of the outbreak / host bacteria concentration at the beginning of infection.

[0068] Incubation period: After inoculation of the oncogenic Enterobacter phage RDP-QEC-24001, the titer did not change significantly after 3 hours, indicating that its incubation period is about 3 hours: within 3-20 hours after the phage infects the host bacteria, the number of phages increases sharply, and it can be seen that the lysis period of the phage is about 17 hours; in the following 3 hours, the number of phages remains basically unchanged and enters a stable growth period. Finally, the average lysis amount is calculated to be 32 PFU / infected cell.

[0069] Example 6: Lysis rate experiment

[0070] 1. Experimental methods

[0071] Under sterile conditions, dilute the freshly grown host bacterial suspension to 1×10 6 CFU / mL, 10 8 , 10 7 , 10 6 The phage with PFU / mL concentration was mixed evenly with the bacterial solution with a fixed concentration, and incubated at 37°C and 170r / min for 15 minutes. After incubation, 100μL of each gradient was spread on the nutrient agar plate and placed at 37°C for 24 hours. Each gradient was repeated twice. Plates with 30-300 colonies were selected for counting. The action trend of different titers of phages and host bacteria was plotted and the lysis efficiency of phages was calculated.

[0072] Phage lysis rate = (1-the number of colonies in the treatment group / the number of colonies in the control group) × 100%.

[0073] The results are shown in Table 2.

[0074] 2. Experimental results and analysis.

[0075] Table 2. Experimental results of cleavage rate

[0076]

[0077] According to calculation, the lysis rate of the bacteriophage RDP-QEC-24001 is 95.37%, which has a good lysis effect on the host and is suitable for use in the breeding process.

[0078] Example 7: In vivo efficacy study of carcinogenic Enterobacteriaceae phage RDP-QEC-24001 in chickens

[0079] 1. Experimental methods

[0080] (1) Carcinogenic Enterobacteriaceae and their phage activation

[0081] The carcinogenic Enterobacter QT-24001 was streaked into LB medium and cultured at 37°C for 24 hours, then streaked into LB medium again and cultured at 37°C for 24 hours. The carcinogenic Enterobacter QT-24001 was inoculated with the shaken carcinogenic Enterobacter QT-24001 at a 2% inoculum, cultured at 37°C for 24 hours, and centrifuged to filter the membrane for later use.

[0082] (2) Activity detection of carcinogenic Enterobacterium QT-24001

[0083] Under sterile conditions, scrape the colonies of Enterobacter QT-24001 on the LB medium, place them in 20 mL of normal saline, shake them to disperse them, then dilute them 10 times with normal saline, select the appropriate concentration to coat the plate, culture them at 37°C for 24 hours, and calculate their content. Place the samples in a 4°C refrigerator for later use.

[0084] (3) Chicken embryo inoculation

[0085] The chicken embryos were divided into groups of 14 days old, with 15 in each group. The inoculation was performed by air chamber inoculation, with an inoculation dose of 1.0×10 4 CFU / piece (inoculation volume is 0.1mL), simulating the process of breeder farms being exposed to pathogenic bacteria.

[0086] In a sterile clean bench, use alcohol cotton balls to completely wipe and disinfect the chicken embryos, use sterile surgical forceps to drill a small hole at the top of the chicken embryo air chamber, use a sterile 1mL syringe to take 0.1mL of the corresponding concentration of bacterial solution and inject it into the chicken embryo air chamber, and then seal the air hole with liquid paraffin after disinfection with alcohol cotton balls, and then put it back in the automatic incubator for incubation. The groups are shown in Table 3. Among them, each QT-24001 challenge group was inoculated with 1.0×10 5 cfu pathogenic bacteria QT-24001 0.1mL, RDP-QEC-24001 treatment group each inoculated 1.0×10 5 cfu pathogenic bacteria QT-24001 0.1mL, negative control group each inoculated with 0.9% NaCl 0.1mL 。

[0087] Table 3 Chicken embryo challenge vaccination grouping

[0088] Grouping Virus attack amount cfu / piece QT-24001 virus attack group <![CDATA[10 4 cfu / piece]]> RDP-QEC-24001 treatment group <![CDATA[10 4 cfu / piece]]> Negative control group 0.9% NaCl 0.1mL

[0089] (4) Observation after vaccination

[0090] After the chicks hatched, they were raised in cages according to groups. The mental state and disease incidence of the chicks in each group were observed every 12 hours. The RDP-QEC-24001 treatment group was gavage-administered with carcinogenic Enterobacteriaceae phage for protection, and the number of chick deaths was counted for 7 consecutive days.

[0091] (5) Protection against carcinogenic Enterobacteriaceae phage RDP-QEC-24001

[0092] After 24 hours of incubation, each mouse in the QT-24001 challenge group was gavaged with 0.1 mL of 0.9% NaCl, and each mouse in the RDP-QEC-24001 treatment group was gavaged with 10 9 pFU / mL RDP-QEC-240010.1mL, and the negative control group was gavaged with 0.9% NaCl 0.1mL each for three consecutive days.

[0093] Table 4 Grouping of chicken embryo administration

[0094] Grouping Therapeutic dose cfu / unit QT-24001 virus attack group 0.9% NaCl 0.1mL RDP-QEC-24001 treatment group <![CDATA[1.0×10 8 PFU / piece]]> Negative control group 0.9% NaCl 0.1mL

[0095] 2. Experimental results and analysis

[0096] Survival rate test: The survival rate of the chicks after treatment and without treatment was used to determine whether the phage was effective. The initial number of chicks in the QT-24001 challenge group was 11, the initial number of chicks in the RDP-QEC-24001 treatment group was 11, and the initial number of chicks in the negative control group was 14. The results are shown in Tables 5 and 6.

[0097] Table 5 Hatching rate results

[0098] QT24001 virus attack group RDP-QEC-24001 treatment group Negative control group Hatching rate (%) 73.3 73.3 93.3 Dead embryo(piece) 4 4 1

[0099] Table 6 Results of the number of deaths in seven days

[0100]

[0101] In summary, it can be seen from Table 5 that the hatching rate of 73.3% in the RDP-QEC-24001 treatment group is the same as that in the QT-24001 challenge group, which is lower than the hatching rate of 93.3% in the negative control group, indicating that the carcinogenic Enterobacter QT-24001 has a significant lethal effect on chicken embryos. At the same time, the influence of the quality of chicken embryos on the next experiment can also be ruled out. The remaining chicken embryos are subjected to the next experiment according to the group.

[0102] Combined with Table 6, it can be seen that the negative control group did not get sick, the chickens were in a healthy mental state, and their eating, drinking and defecation were normal; the QT-24001-challenged group had a depressed mental state, the umbilical cords of the sick chicks were red and swollen, the abdomen was swollen, and the feces were thin and yellow-white; after phage treatment, the mental state recovered, the incidence rate decreased, and the mortality rate decreased by about 18.2%, which proves that the bacteriophage RDP-QEC-24001 is very effective and greatly reduces the mortality rate of chicks.

[0103] It should be pointed out that the specific implementation methods are only representative examples of the present invention. Obviously, the technical solution of the present invention is not limited to the above-mentioned embodiments, and there are many variations. Those skilled in the art who can obtain the invention clearly disclosed in the present invention or without objection based on the written description of the document should be considered as the scope of protection of this patent.

Claims

1. A strain of Enterobacter cancerogenus phage RDP-QEC-24001, characterized in that: The lytic oncogenic Enterobacteriaceae phage RDP-QEC-24001 was deposited in the General Microbiology Center of China National Microbiological Culture Collection Administration on September 23, 2024, with the deposit number CGMCC No.46191.

2. A bacteriophage composition, characterized in that: It comprises the lytic carcinogenic Enterobacteriaceae phage RDP-QEC-24001 as claimed in claim 1.

3. Use of the oncogenic Enterobacteriaceae-lysing bacteriophage RDP-QEC-24001 according to claim 1 or the bacteriophage composition according to claim 2 in the preparation of products for preventing and / or treating livestock and poultry diseases caused by oncogenic Enterobacteriaceae.

4. Use of the oncogenic Enterobacteriaceae-lysing bacteriophage RDP-QEC-24001 according to claim 1 or the bacteriophage composition according to claim 2 in the preparation of a product for killing and / or inhibiting oncogenic Enterobacteriaceae.

5. A bacteriophage pharmaceutical preparation, characterized in that: The active ingredient comprises the carcinogenic Enterobacteriaceae phage RDP-QEC-24001 as claimed in claim 1 or the phage composition as claimed in claim 2.

6. The bacteriophage pharmaceutical preparation according to claim 5, characterized in that The concentration of the lytic carcinogenic Enterobacteriaceae phage RDP-QEC-24001 is at least 10 9 pfu / mL.

7. A drinking water additive, characterized in that: The active ingredient comprises the carcinogenic Enterobacteriaceae phage RDP-QEC-24001 as claimed in claim 1 or the phage composition as claimed in claim 2.

8. A feed additive, characterized in that: The active ingredient comprises the carcinogenic Enterobacteriaceae phage RDP-QEC-24001 as claimed in claim 1 or the phage composition as claimed in claim 2.

9. A disinfectant, characterized in that: The active ingredient comprises the carcinogenic Enterobacteriaceae phage RDP-QEC-24001 as claimed in claim 1 or the phage composition as claimed in claim 2.

10. A cleaning agent, characterized in that: The active ingredient comprises the carcinogenic Enterobacteriaceae phage RDP-QEC-24001 as claimed in claim 1 or the phage composition as claimed in claim 2.

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