Acinetobacter baumannii phage and application thereof

Abstract

The invention discloses an acinetobacter baumannii bacteriophage and an application thereof. The acinetobacter baumannii phage disclosed by the invention is vBMZM2AB-P, and the preservation number of the acinetobacter baumannii phage is CCTCC (China Center for Type Culture Collection) NO: M20241199. The acinetobacter baumannii bacteriophage is short in incubation period, high in lysis activity, good in stability and high in environmental endurance capacity, a new bacteriophage is provided for prevention, control or treatment of acinetobacter baumannii, and a new scheme and approach are provided for treatment of multi-drug-resistant acinetobacter baumannii.

Description

Technical Field

[0001] The present application relates to the field of bacteriophage technology, and in particular to a bacteriophage of Acinetobacter baumannii and its application. Background Art

[0002] Acinetobacter baumannii is an important pathogen of nosocomial infection, which can cause hospital-acquired infections such as bacteremia, urinary tract infection and ventilator-associated pneumonia. It can quickly develop antibiotic resistance, which has led to the emergence of multidrug-resistant and pan-resistant Acinetobacter baumannii (MDRAB and PDRAB) in just a few decades. Multiple resistance mechanisms limit the clinical treatment of Acinetobacter baumannii, among which β-lactamase is the most common. The effectiveness of existing antibiotics in treating resistant Acinetobacter baumannii is becoming increasingly limited. There is an urgent need to find new methods to replace antibiotics in the treatment of bacterial infections.

[0003] Bacteriophages are bacterial viruses that have been shown to have great potential in treating bacterial infections by replacing traditional antibiotic therapy. 31 Bacteriophages are a huge natural antimicrobial drug library. Bacteriophages have strong host specificity and are highly efficient in trace amounts. The lysis spectrum can be broadened by combining phage cocktails, effectively reducing the development of phage resistance in pathogenic bacteria. Studies have shown that phage-antibiotic combination (PAC) therapy may be a feasible strategy for treating infections caused by high-level multidrug-resistant Acinetobacter baumannii or other resistant bacteria. Studies have found that phage and antibiotic resistance phenotypes evolve independently to a large extent, indicating that the use of antibiotics is unlikely to drive changes in phage resistance, revealing the broad prospects of phage therapy and phage-antibiotic combination therapy. Phages have shown an important role in clinical treatment that cannot be ignored, so it is very necessary to isolate new phages and study them.

[0004] Several in-depth studies have shown that the use of phages and antibiotics in synergy has shown significant potential in the treatment of biofilm-forming Acinetobacter baumannii infections, which is very promising. Wang et al. found that when colistin was used in combination with the Acinetobacter baumannii phage Phab24, the apparent MIC (minimum inhibitory concentration) of colistin was reduced. Studies have shown that bacterial resistance to phages may be accompanied by a "trade-off" mechanism, which increases resistance to phages by reducing their own virulence and increasing sensitivity to antibiotics. Therefore, the synergistic effect of phages and antibiotics can exert a better therapeutic effect. With the in-depth study of the interaction between phages and bacteria, the application prospects of phage therapy in the treatment of bacterial infections are becoming increasingly broad.

[0005] In short, the development of new Acinetobacter baumannii phages with better performance in all aspects plays an important role and value in the treatment of Acinetobacter baumannii infections. Summary of the invention

[0006] The purpose of the present application is to provide a new Acinetobacter baumannii phage and its application.

[0007] This application adopts the following technical solutions:

[0008] The first aspect of the present application discloses a strain of Acinetobacter baumannii phage, which is vB_MZM_2AB-P, and its deposit number is CCTCC NO: M 20241199.

[0009] It should be noted that the key to this application is that a new phage vB_MZM_2AB-P that can infect multidrug-resistant Acinetobacter baumannii has been isolated. Its whole genome similarity with the closest Acinetobacter phages DMU1 and SH-Ab 15497 is 94.18% and 92.8%, respectively, and it belongs to a new species in evolutionary classification. The vB_MZM_2AB-P of this application has strong host specificity and temperature tolerance, and can still maintain activity at a temperature of 80°C. At the same time, the phage also exhibits good storage stability and a wide pH tolerance range. The phage vB_MZM_2AB-P of this application has a fast adsorption time, an incubation period of 10 minutes, and can lyse bacteria within 50 minutes, showing a high lytic activity. In summary, the Acinetobacter baumannii phage vB_MZM_2AB-P of the present application has the advantages of short incubation period, high lytic activity, good stability, strong environmental tolerance, and novel genetic background. It provides a new phage with better performance in all aspects for the treatment of Acinetobacter baumannii infection, and also provides more resources for the combination of "phage cocktails".

[0010] Preferably, the complete genome of the Acinetobacter baumannii phage is the sequence shown in SEQ ID NO.1.

[0011] The second aspect of the present application discloses the use of the Acinetobacter baumannii phage of the present application in the preparation of an agent for preventing, controlling or killing Acinetobacter baumannii.

[0012] The third aspect of the present application discloses a reagent for preventing, controlling or killing Acinetobacter baumannii, wherein the reagent contains the Acinetobacter baumannii phage of the present application.

[0013] It can be understood that the Acinetobacter baumannii phage of the present application can specifically lyse the Acinetobacter baumannii phage, and therefore can be used to prepare reagents for preventing, controlling or killing Acinetobacter baumannii. For example, when treating hospital sewage, the reagents of the present application can be used to prevent, control or kill Acinetobacter baumannii therein.

[0014] The fourth aspect of the present application discloses the use of the Acinetobacter baumannii phage of the present application in the preparation of a drug for preventing or treating a disease caused by Acinetobacter baumannii.

[0015] The fifth aspect of the present application discloses a drug for preventing or treating a disease caused by Acinetobacter baumannii, wherein the drug contains the Acinetobacter baumannii phage of the present application.

[0016] It can be understood that the Acinetobacter baumannii phage of the present application can specifically lyse the Acinetobacter baumannii phage, and thus can be used to prepare drugs for preventing or treating diseases caused by Acinetobacter baumannii.

[0017] Preferably, the medicine of the present application further contains a pharmaceutically acceptable carrier and / or excipient.

[0018] It can be understood that the drug of the present application can be prepared into different dosage forms according to needs. When selecting the corresponding carrier and / or excipient, as long as it can help the Acinetobacter baumannii phage of the present application to exert its effect, the specific carrier or excipient can refer to the existing phage drugs, which will not be repeated here.

[0019] The beneficial effects of this application are:

[0020] The Acinetobacter baumannii phage of the present application has a short incubation period, high lytic activity, good stability, and strong environmental tolerance, providing a new phage for the prevention, control or treatment of Acinetobacter baumannii, and providing a new solution and approach for the treatment of multidrug-resistant Acinetobacter baumannii. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 1 is a diagram showing the plaque morphology and microscopic morphology observation results of the bacteriophage vB_MZM_2AB-P in the examples of the present application, wherein Figure A is a plaque photograph and Figure B is a transmission electron microscope observation diagram;

[0022] Figure 2 1 is the test result of biological properties of bacteriophage vB_MZM_2AB-P in the embodiment of the present application, wherein Figure A is the temperature stability test result, Figure B is the acid-base stability test result, Figure C is the storage stability test result, Figure D is the optimal adsorption time test result, and Figure E is the optimal infection multiplicity test result. The bacteriophage and bacteria are mixed in a ratio of 10:1, 1:1, 1:10, 1:1000, and Figure F is a one-step growth curve;

[0023] Figure 3 is the genome structure diagram of bacteriophage vB_MZM_2AB-P in the examples of the present application;

[0024] Figure 4This is the complete genome evolution tree of bacteriophage vB_MZM_2AB-P in the examples of this application.

[0025] The Acinetobacter baumannii phage of the present application, with the Latin name Acinetobacter phage vB_MZM_2AB-P, was deposited in the China Center for Type Culture Collection on June 13, 2024, with the address: Wuhan University, No. 299, Bayi Road, Wuchang District, Wuhan City, Hubei Province, with the deposit number CCTCC NO: M20241199. DETAILED DESCRIPTION

[0026] The present application is further described in detail below through specific examples. The following examples are only used to further illustrate the present application and should not be construed as limiting the present application.

[0027] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources, and the experimental methods used in the following examples are conventional methods unless otherwise specified.

[0028] Example

[0029] 1. Materials and Methods

[0030] 1. Isolation and purification of bacteriophage

[0031] In this experiment, the multidrug-resistant strain Acinetobacter baumannii 2AB (provided and preserved by Hainan Normal University) was used as an indicator bacteria to isolate and identify bacteriophages. Sewage samples were collected from the river under the overpass in Longhua District, Haikou City, Hainan Province. The sewage samples were centrifuged at 10,000 rpm for 15 minutes at 4°C. 200 mL of the supernatant was added to 3 times LB culture medium containing indicator bacteria. After incubation at 37°C for 18-24 hours, the supernatant was centrifuged at 10,000 rpm for 15 minutes. After filtering through a bacterial filter with a pore size of 0.22 μm, the bacteriophages were cultured using the double-layer plate method. The bacteriophages were purified multiple times until plaques of uniform size and morphology appeared. References DiLallo, G., et al., J Basic Microbiol, 2014.54(11): p.1210-21.

[0032] 2. Phage host spectrum determination

[0033] The lysis spectrum was determined using the test strains. 100 μL of bacterial suspension of different strains was mixed with LB semi-solid medium and poured onto the LB plate. After the plate solidified, 3 μL of phage was spotted on it. At the same time, an equal volume of sterile water was spotted as a control. The next day, the plate was observed for plaques. Reference Peng, Q., et al., Microorganisms, 2020.8(4): p.542. The strains that the phage can lyse were judged based on the presence or absence of plaques.

[0034] The test strains used for phage host spectrum determination in this example are shown in Table 1.

[0035] Table 1 Test strains

[0036]

[0037]

[0038] 3. Phage morphology observation

[0039] In order to identify the morphology of the phage, the fresh elution of the phage was collected and added to a carbon-coated copper grid, and negatively stained with 2% phosphotungstic acid. The negative staining method was referred to Ding, Y., et al., Virus Res, 2023.326: p.199054. The samples were sent to Beijing Zhongke Baice Technology Service Co., Ltd., and the morphology of the phage particles was observed using a transmission electron microscope (TEM, JEM-1400, JEOL, Japan) at a voltage of 100 kV. The size of the phage head and tail was measured using the software ImageJ.

[0040] 4. Phage stability assay

[0041] The phage suspension was incubated at 30, 40, 50, 60, 70, and 80°C for 30 minutes to determine its thermal stability, and the titer was determined after cooling to room temperature. The phage at room temperature was used as a control and the experiment was repeated three times. The phage suspension was incubated in a solution of pH 1.0, 3.0, 5.0, 7.0, 9.0, and 11.0 at room temperature for 30 minutes to determine the acid-base stability. The initial pH value of the suspension was used as a control and the experiment was repeated three times. The phage suspension was placed in an environment of -20, 4, and 28°C, and the phage titer was determined after storage for 1 week, 2 weeks, 1 month, 2 months, 3 months, 5 months, and 8 months. The initial concentration was used as a control and the experiment was repeated three times. References Peng, Q., et al., Microorganisms, 2020.8(4): p.542.

[0042] 5. Determination of optimal phage adsorption time

[0043] Take phage and bacterial solution in a 1:1 ratio and mix them evenly. Adsorb for different time periods and centrifuge at 10,000 rpm for 1 min. Determine the phage titer in the supernatant. Use sterile culture medium as a control and determine the optimal phage adsorption time based on the titer.

[0044] 6. Optimal Multiplicity of Infection (MOI) Analysis

[0045] In order to determine the ability of different concentrations of phage to lyse host bacteria, exponentially growing Acinetobacter baumannii 2AB was used. The phage and bacteria were mixed in a ratio of 10, 1, 0.1, 0.01, and 0.001, respectively, and allowed to stand at 37°C for adsorption for 5 minutes. Then centrifuged at 10,000 rpm for 1 minute, and the unadsorbed phage was filtered out. The precipitate was resuspended in 50 mL of fresh LB medium and cultured in a shaking incubator at 37°C. Bacterial culture without the addition of phage was used as a control. The optical density (OD 595nm ). Reference, Peng, Q., et al.,. Sci Rep, 2023.13(1): p.9815.

[0046] 7. One-step growth curve of bacteriophage

[0047] In order to study the incubation period and lysis amount of phage, take the bacterial solution in the logarithmic growth phase and mix it with the phage at a multiplicity of infection (MOI) of 1.0, and let it stand at 30℃ for 5 minutes to allow the phage to adsorb to the bacteria. Centrifuge at 10,000rpm for 1 minute at room temperature to remove the unadsorbed phage, discard the supernatant, resuspend the precipitate in 50mL of LB medium and start timing. Take samples every 30 minutes and measure their OD 595 The concentration changes under different wavelengths, the titer was measured, the experiment was repeated three times, the results were recorded, and a one-step growth curve was drawn according to the method described in the report. References: Cao, Y., et al., Arch Virol, 2021.166(2): p.413-426.

[0048] 8. Extraction, sequencing and genome analysis of phage DNA

[0049] Phage genomic DNA was extracted according to the research method of Peng et al., Peng, Q., et al., Sci Rep, 2023.13(1): p.9815. The whole genome of phage DNA was sequenced using the Illumina Hiseq sequencing platform and FastQC V0.11.2 software, and the raw sequencing data of phage was cut and spliced ​​using Trimmomatic V0.36 software to obtain accurate and effective measurement data. The complete fragment was obtained using SPAdes-3.5.0 software. Coding sequences (CDSs) in the genome were predicted using FGENESV0 (Softberry, http: / / linux1.softberry.com) and visualized using CGView (https: / / proksee.ca / projects / new), with references to Bardina, C., et al., Front Microbiol, 2016.7: p.545; Stothard, P., JRGrant, and G. Van Domselaar, Brief Bioinform, 2019.20(4): p.1576-1582. The basic local alignment algorithm search tool (BLAST) was used to search each predicted gene in the NCBI non-redundant protein sequence (NR) and CDD databases (https: / / www.ncbi.nlm.nih.gov). The sequences and functional domains of the predicted proteins were functionally annotated using the Pfam database. tRNAs encoding genes were searched using tRNAscan-SE 2.0 (http: / / lowelab.ucsc.edu / tRNAscan-SE / index.html), and references were made to Schattner, P., AN Brooks, and TM Lowe, Nucleic Acids Res, 2005.33 (Web Server issue): p.W686-9. Tandem Repeat Finder software was used to search for repeat sequences in phage genomes (https: / / tandem.bu.edu / trf / trf.basic.submit.html), and virulence search programs (http: / / www.hpabioinfotools.org.uk / pise / virfactfind_small.html) were used to search for virulence genes.Phage genome sequences with a similarity greater than 70% with the sequenced phage genome were selected from the NCBI database, and a heat map was generated using the OrthoANl values ​​calculated by the OAT software (https: / / www.ezbiocloud.net / tools / orthoani). Reference: Lee, I., et al., Int J Syst Evol Microbiol, 2016. 66(2): p. 1100-1103.

[0050] 2. Results and Analysis

[0051] 1. Phage morphology observation

[0052] Using Acinetobacter baumannii 2AB as an indicator bacterium, a bacteriophage was screened and purified from the sewage in the river under the overpass in Longhua District, Hainan Province, and was named vB_MZM_2AB-P. After 20 hours of constant temperature culture, the bacteriophage formed a plaque with a central diameter of 1 mm and no halo on the Acinetobacter baumannii 2AB plate. The results are as follows Figure 1 As shown in Figure A.

[0053] 2. Transmission electron microscopy observation of phage particles

[0054] Transmission electron microscopy observation of phage particles showed that phage vB_MZM_2AB-P has an icosahedral head with a diameter of about 55 nm, a tail of about 121 nm in length and 9 nm in width, as shown in Figure 2. Figure 1 As shown in Figure B. Based on the morphology of the phage particles, this phage belongs to a siphovirus.

[0055] 3. Phage host spectrum determination

[0056] Bacteriophage vB_MZM_2AB-P has strong host specificity. Among the 24 strains tested, vB_MZM_2AB-P can only infect Acinetobacter baumannii 2AB and ATCC-19606, as shown in Table 2. Strong host specificity improves the safety of phages in clinical treatment and avoids interference with other beneficial bacteria.

[0057] Table 2 Phage host spectrum determination results

[0058] Strain number Bacteria Phage sensitivity 2AB Acinetobacter baumannii + 4AB Acinetobacter baumannii - ATCC-19606 Acinetobacter baumannii + ATCC-17978 Acinetobacter baumannii - 6AB Acinetobacter baumannii - 7AB Acinetobacter baumannii - CSV Salmonella enterica - RSV Salmonella enterica - NTV Salmonella enterica - Xu1 Klebsiella pneumoniae - 2106 Klebsiella pneumoniae - 0915 Klebsiella pneumoniae - 1025 Klebsiella pneumoniae - ATCC BAA-1705 Klebsiella pneumoniae - ATCC 13883 Klebsiella pneumoniae - CMCC 40396 Escherichia coli - 40102 Escherichia coli - 40482 Escherichia coli - CMCC 6538G3 Staphylococcus aureus - TAO-1 Staphylococcus aureus - XH Pseudomonas - CMCC 63501 Bacillus subtilis - GR-8 Bacillus pumilus - ATCC 17802 Vibrio parahaemolyticus -

[0059] 4. Phage stability assay

[0060] The results of thermal stability showed that the survival rate of phage vB_MZM_2AB-P was 24.9% at a temperature of 60°C, and it could still maintain 12.4% activity at 70°C. Figure 2The pH stability results show that the phage vB_MZM_2AB-P is stable at neutral pH and can maintain activity in an alkaline environment. When pH = 11, it still has 11.9% activity, as shown in Figure A. Figure 2 As shown in Figure B. The storage stability results show that the phage vB_MZM_2AB-P has good storage stability. After being stored at -20℃, 4℃, and 28℃ for 1 month, it still has a survival rate of more than 77%, and after being stored for 3 months, it can still maintain a survival rate of more than 37%. After 150 days, the survival rate of phage vB_MZM_2AB-P at -20℃ was 25.2%, and the survival rate of phage vB_MZM_2AB-P at 4℃ was 18.4%. It was not until the 240th day that the phages stored at various temperatures lost their activity, as shown in Figure 2. Figure 2 As shown in Figure C. In comparison, it has better storage stability at 4°C and -20°C. Bacteriophage vB_MZM_2AB-P exhibits good thermal stability and storage stability, which can greatly reduce the cost of transportation and storage in practical applications.

[0061] 5. Determination of optimal phage adsorption time

[0062] When the phage vB_MZM_2AB-P was adsorbed for 5 min, the phage content in the mixed solution was the lowest, that is, the infection effect of the phage vB_MZM_2AB-P and the host bacteria was the best when they were adsorbed for 5 min. Figure 2 As shown in Figure D, 5 min is the optimal adsorption time for the phage.

[0063] 6. Optimal Multiplicity of Infection (MOI) Analysis

[0064] When the MOI was 1, the titer of phage vB_MZM_2AB-P was the highest, which was 1.18×10 7 CFU / mL, so MOI = 1 is the optimal multiplicity of infection, such as Figure 2 As shown in Figure E. This phage strain showed a significant inhibitory effect, and even the lowest MOI = 0.001 was able to significantly inhibit the growth of the host bacteria. Studies have shown that increasing the amount of phage has limited effect on enhancing phages that have high lysis capabilities. Therefore, increasing the amount of phage to deal with the emergence of phage resistance in bacteria is not an ideal strategy, and exploring phage cocktails is more realistic.

[0065] 7. One-step growth curve of bacteriophage

[0066] The one-step growth curve of phage vB_MZM_2AB-P showed that the incubation period of the phage was 10 min, the lysis period lasted about 50 min, and the highest titer of the phage was 1.12×10 7PFU / mL, the lysis amount is 7.32pfu / cell, such as Figure 2 As shown in Figure F, it can be seen that bacteriophage vB_MZM_2AB-P has the characteristics of short incubation period and large lysis amount.

[0067] 8. Whole genome analysis of bacteriophage vB_MZM_2AB-P

[0068] The genome of bacteriophage vB_MZM_2AB-P is a linear double-stranded DNA with a genome size of 43664bp and a G+C content of 47.76%. The Genbank number is PP091972. The bacteriophage genome encodes a total of 65 open reading frames (ORFs), of which 6 are forward transcribed and 59 are reverse transcribed. Figure 3 As shown. A total of 57 proteins are from the baumannii phage, while the other 8 proteins are unique to the phage, and no similar proteins have been found. The protein function prediction results show that 49 are predicted as hypothetical proteins and 16 are predicted as known functional proteins. Two ORFs are annotated as nucleic acid metabolism-related proteins, including gp5 and gp12, which encode DNA polymerase and superfamily II DNA or RNA helicase, respectively. These two enzymes play a catalytic role in the replication of phage genome DNA. 9 ORFs are annotated as phage structural proteins, including gp15, gp22, gp26, gp27, gp28, gp29, gp32, gp34, and gp36, which encode tail protein, tape measure protein, major tail structural protein, tail terminal protein, structural protein, structural protein, capsid protein, head protein, and portal protein, respectively. Among them, three ORFs were annotated as phage packaging proteins, including gp33, gp37, and gp41, encoding DNA packaging proteins, large subunits of terminase, and small subunits of terminase, respectively. Two ORFs were annotated as cell lysis-related proteins, including gp39 and gp40, encoding perforin and lytic enzymes, respectively. Lytic enzymes are highly specific to target bacteria, do not affect mammalian host cells, and have low toxicity risks to human cells, which greatly improves safety compared to traditional antibiotic therapy. The genome of bacteriophage vB_MZM_2AB-P contains a gene encoding tRNA-Arg, the anticodon TCT, and three repeat sequences, indicating that vB_MZM_2AB-P has its own mechanism for synthesizing proteins. Bacteriophage vB_MZM_2AB-P has a terminal repeat region of about 26bp at each end of the genome, and its packaging mechanism may involve direct terminal repeats (DTR, Direct Terminal Repeats). No antibiotic resistance genes or virulence factors were found in the genome using ResFinder and VFDB, so this phage has good safety for practical use in humans.

[0069] Figure 3 In the figure, different gene modules are marked with different colors, including packaging gene module (blue), nucleic acid metabolism-related gene module (green), structural gene module (orange) and cell lysis-related gene module (pink). Genes with unknown functions are represented in gray.

[0070] The complete genome of the bacteriophage vB_MZM_2AB-P in this example is the sequence shown in SEQ ID NO.1.

[0071] SEQ ID NO.1:

[0072]

[0073] 9. Phage Comparative Genomic Analysis

[0074] The similarity heat map results between the whole genomes of phage vB_MZM_2AB-P showed that vB_MZM_2AB-P and Acinetobacter phages DMU1, SH-Ab 15497, and pB23 were in the same evolutionary branch, such as Figure 4 As shown. It has the closest relationship with DMU1, with a similarity of 94.18% (Query Cover = 99%, Per.Ident = 95.13%) and OrthoANI = 94.81%. The similarity with SH-Ab 15497 is 92.8% (Query Cover = 98%, Per.Ident = 94.7%), and OrthoANI = 94.4%. According to the phage classification method of Dann Turner et al., two phages with genome similarity higher than 95% are classified as the same species, and phages with similarity higher than 70% are classified as the same genus. The whole genome BLASTn similarity of vB_MZM_2AB-P with DMU1 and SH-Ab 15497 is less than 95%, and it belongs to a new species in evolutionary classification. The BLASTn similarities with Acinetobacter phages pB23, Barton, and JeffCo were between 68.01% and 18.53%, but they showed no similarity with other phages, and belonged to different genera in evolutionary classification. At present, the Acinetobacter phages DMU1, SH-Ab 15497, pB23, Barton, and JeffCo, which are closely related to vB_MZM_2AB-P, belong to the kingdom Heunggongvirae; the class Caudoviricetes of the phylum Uroviricota, and there is no more specific classification under the class Caudoviricetes. Therefore, the entire evolutionary branch of Acinetobacter baumannii phages vB_MZM_2AB-P, DMU1, SH-Ab 15497, pB23, Barton, and JeffCo can be classified as a new genus under the siphovirus of the kingdom Heunggongvirae; the class Caudoviricetes of the phylum Uroviricota, with a novel genetic background.

[0075] The above contents are further detailed descriptions of the present application in combination with specific implementation methods, and it cannot be determined that the specific implementation of the present application is limited to these descriptions. For ordinary technicians in the technical field to which the present application belongs, several simple deductions or substitutions can be made without departing from the concept of the present application.

Claims

1. A bacteriophage of Acinetobacter baumannii, characterized in that: The Acinetobacter baumannii phage is vB_MZM_2AB-P, and its preservation number is CCTCC NO: M 20241199.

2. The Acinetobacter baumannii phage according to claim 1, characterized in that: The complete genome of the Acinetobacter baumannii phage is the sequence shown in SEQ ID NO.

1.

3. Use of the Acinetobacter baumannii phage according to claim 1 or 2 in the preparation of an agent for preventing, controlling or killing Acinetobacter baumannii.

4. A reagent for preventing, controlling or killing Acinetobacter baumannii, characterized in that: The reagent contains the Acinetobacter baumannii phage according to claim 1 or 2.

5. Use of the Acinetobacter baumannii phage according to claim 1 or 2 in the preparation of a medicament for preventing or treating a disease caused by Acinetobacter baumannii.

6. A drug for preventing or treating a disease caused by Acinetobacter baumannii, characterized in that: The medicine contains the Acinetobacter baumannii phage according to claim 1 or 2.

7. The drug according to claim 6, characterized in that: The medicine also contains pharmaceutically acceptable carriers and / or excipients.

Images