Marine antibacterial peptide and application thereof

Abstract

The invention relates to the technical field of antibacterial peptides, and particularly discloses a marine antibacterial peptide and application thereof, and the amino acid sequence of the marine antibacterial peptide is as shown in SEQ ID NO.1: MWKLPKWRNGRRRGFKIPRW. The marine antibacterial peptide CD109 provided by the invention has an inhibition effect on staphylococcus aureus, acinetobacter baumannii, pseudomonas aeruginosa and klebsiella pneumoniae, and has extremely low cytotoxicity.

Description

Technical Field

[0001] The present invention relates to the technical field of antimicrobial peptides, and in particular to a marine antimicrobial peptide and application thereof. Background Art

[0002] Antibiotic resistance has a great impact on people's lives. Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa account for the majority of antibiotic-resistant infections. Therefore, there is an urgent need to explore new antimicrobial drugs to cope with the growing resistance of pathogens. Among them, antimicrobial peptides have attracted widespread attention as potential new antibiotics.

[0003] Antimicrobial peptides, also known as antimicrobial peptides, are widely distributed in organisms and are part of the natural immune defense system. Antimicrobial peptides have become an important direction for clinical drug discovery. Unlike conventional antibiotics, antimicrobial peptides are protein products encoded by a specific gene and therefore have a unique antimicrobial mechanism. Despite this, the clinical application of antimicrobial peptides still faces challenges, such as strong cytotoxicity, poor environmental stability, and lack of selectivity for specific strains.

[0004] The existing antimicrobial peptides generally have the problem of having a wide antibacterial range but poor antibacterial effect, or having a good antibacterial effect but a single antibacterial spectrum. Therefore, it is of great significance to develop a new antimicrobial peptide with a broad-spectrum and efficient antibacterial effect. Summary of the invention

[0005] In order to develop an antibacterial peptide with a broad-spectrum antibacterial effect, the present invention provides a marine antibacterial peptide and its application. The marine antibacterial peptide CD109 provided by the present invention can effectively inhibit Staphylococcus aureus, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, and has the potential to prepare antibacterial products.

[0006] The present invention provides a marine antimicrobial peptide CD109, the amino acid sequence of which is shown in SEQ ID NO.1: MWKLPKWRNGRRRGFKIPRW.

[0007] The marine antimicrobial peptide CD109 provided by the present invention can effectively inhibit Staphylococcus aureus, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, with good antibacterial effect and a wide antibacterial spectrum. The marine antimicrobial peptide CD109 has a minimum inhibitory concentration of 2 μg / mL for Staphylococcus aureus, a minimum inhibitory concentration of 32 μg / mL for Acinetobacter baumannii, a minimum inhibitory concentration of 128 μg / mL for Pseudomonas aeruginosa, and a minimum inhibitory concentration of 128 μg / mL for Klebsiella pneumoniae, and has the potential to prepare antibacterial products.

[0008] The present invention also provides an antimicrobial peptide CD109C, which is obtained by modifying the C-terminus of the marine antimicrobial peptide CD109 through amidation. The amino acid sequence of the antimicrobial peptide CD109C is: MWKLPKWRNGRRRGFKIPRW-NH2. The molecular formula of the antimicrobial peptide is C 125 H 195 N 43 O 21 S.

[0009] The present invention provides an application of the marine antimicrobial peptide CD109 or antimicrobial peptide CD109C in the preparation of an antimicrobial product, wherein the antimicrobial product is used to inhibit Staphylococcus aureus, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae-like bacteria, and has a good antimicrobial effect and a broad antimicrobial spectrum.

[0010] Furthermore, the antibacterial product is a medicine or an antibacterial agent.

[0011] Furthermore, the antibacterial product uses marine antibacterial peptide CD109 or antibacterial peptide CD109C as the only active ingredient.

[0012] Furthermore, the minimum inhibitory concentration of the marine antimicrobial peptide CD109 against Staphylococcus aureus is 2 μg / mL, the minimum inhibitory concentration against Acinetobacter baumannii is 32 μg / mL, the minimum inhibitory concentration against Pseudomonas aeruginosa is 128 μg / mL, and the minimum inhibitory concentration against Klebsiella pneumoniae is 128 μg / mL.

[0013] Furthermore, the minimum inhibitory concentration of the antimicrobial peptide CD109C against Staphylococcus aureus is 4 μg / mL, the minimum inhibitory concentration against Acinetobacter baumannii is 8 μg / mL, the minimum inhibitory concentration against Pseudomonas aeruginosa is 16 μg / mL, and the minimum inhibitory concentration against Klebsiella pneumoniae is 16 μg / mL.

[0014] Furthermore, the antibacterial agent is obtained by dissolving marine antimicrobial peptide CD109 or antimicrobial peptide CD109C in sterile water.

[0015] Furthermore, the concentration of antimicrobial peptides in the antibacterial agent is 2 μg / mL to 128 μg / mL.

[0016] Furthermore, the medicine also includes pharmaceutically acceptable excipients.

[0017] Furthermore, the auxiliary material is any one or a combination of lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil.

[0018] Compared with the prior art, the present invention has the following beneficial effects: The marine antimicrobial peptide CD109 provided by the present invention and the antimicrobial peptide CD109C obtained by C-terminal amidation modification can effectively inhibit Staphylococcus aureus, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, with good antibacterial effect and a wide antibacterial spectrum. The antibacterial effect of the modified antimicrobial peptide CD109C is more significant than that of the marine antimicrobial peptide CD109. The minimum inhibitory concentration of the antimicrobial peptide CD109C for Staphylococcus aureus is 4 μg / mL, the minimum inhibitory concentration for Acinetobacter baumannii is 8 μg / mL, the minimum inhibitory concentration for Pseudomonas aeruginosa is 16 μg / mL, and the minimum inhibitory concentration for Klebsiella pneumoniae is 16 μg / mL. The antimicrobial peptide CD109C has good pH stability and extremely low cytotoxicity. These characteristics make it show extremely high antibacterial value of medical drugs, providing alternative medicinal resources for future clinical treatment against a variety of human pathogens. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0020] Figure 1 MIC values ​​of the original antimicrobial peptide CD109 and the modified antimicrobial peptide CD109C against 7 human pathogens.

[0021] Figure 2 MIC values ​​of antimicrobial peptide CD109C against Acinetobacter baumannii 19606 after incubation for 1 hour at pH 2, pH 7.4, and pH 8.4.

[0022] Figure 3 The results show the cytotoxicity of antimicrobial peptide CD109C on skin keratinocytes HaCat and bronchial epithelial cells BEAS-2B. DETAILED DESCRIPTION

[0023] The specific embodiments of the present invention are described in detail below, but it should be understood that the protection scope of the present invention is not limited by the specific embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the scope of protection of the present invention. The experimental methods described in the embodiments of the present invention are conventional methods unless otherwise specified, and the materials, reagents, etc. used in the following embodiments can be obtained from commercial channels unless otherwise specified.

[0024] The present invention provides a marine antimicrobial peptide CD109 and a modified antimicrobial peptide CD109C having a broad-spectrum antibacterial effect, wherein the amino acid sequence of the marine antimicrobial peptide CD109 is shown in SEQ ID NO. 1, and the amino acid sequence of the antimicrobial peptide CD109C is shown in SEQ ID NO. 2.

[0025] The marine antimicrobial peptide CD109 can effectively inhibit multiple drug-resistant human pathogens. The minimum inhibitory concentration of the marine antimicrobial peptide CD109 against Staphylococcus aureus 12600 is 2 μg / mL, the MIC against Acinetobacter baumannii 19606 is 32 μg / mL, and the MIC against Pseudomonas aeruginosa PAO1 and Klebsiella pneumoniae are both 128 μg / mL.

[0026] The antimicrobial peptide CD109C can effectively inhibit multiple drug-resistant human pathogens, with the minimum inhibitory concentrations of 4 μg / mL, 8 μg / mL, and 16 μg / mL for Staphylococcus aureus 12600, Staphylococcus aureus 33591, and Staphylococcus aureus 33592, respectively, the MICs of 16 μg / mL and 8 μg / mL for Acinetobacter baumannii 19606 and Acinetobacter baumannii 53272, and the MICs of 16 μg / mL and 16 μg / mL for Pseudomonas aeruginosa PAO1 and Klebsiella pneumoniae, respectively. The antimicrobial peptide CD109C has good pH stability, and after incubation for 1 hour under pH2, pH7.4, and pH8.4 conditions, the MIC for Acinetobacter baumannii 19606 remains at 16 μg / mL. CD109C has extremely low cytotoxicity. Skin keratinocytes HaCat and bronchial epithelial cells BEAS-2B still maintained 98.02% and 94.4% survival rates after being treated with 128 μg / mL CD109C for 24 hours. The antimicrobial peptide CD109C shows extremely high antibacterial value as a medical drug and can provide an alternative medicinal resource for future clinical use against multiple drug-resistant pathogens.

[0027] Example 1: A marine antimicrobial peptide CD109 and its modified antimicrobial peptide CD109C.

[0028] In this example, the sequence information of the antimicrobial peptide CD109 was designed, and then prepared by Sangon Biotech Co., Ltd. using solid phase chemical synthesis, with a purity of >95%. Finally, the amino acid sequence of the antimicrobial peptide CD109 was obtained.

[0029] The amino acid sequence of the antimicrobial peptide CD109 is shown in SEQ ID NO.1.

[0030] SEQ ID NO. 1: MWKLPKWRNGRRRGFKIPRW.

[0031] The marine antimicrobial peptide CD109 contains 20 amino acids, and the C-terminus of the sequence is amidated to obtain the antimicrobial peptide CD109C. The amino acid sequence of the antimicrobial peptide CD109C is shown in SEQ ID NO.2.

[0032] SEQ ID NO.2: MWKLPKWRNGRRRGFKIPRWX, X is -NH2, and -NH2 indicates the C-terminal amidation modification of the marine antimicrobial peptide CD109.

[0033] The molecular formula of the antimicrobial peptide CD109C is C 125 H 195 N 43 O 21 S, with a molecular weight of 2668.22 g / mol, a net charge number of 9, carries 9 positive charges, an isoelectric point of 13.01, a normalized hydrophobicity of -0.01, and an amphipathic index of 2.20.

[0034] The protein structure of the marine antimicrobial peptide CD109 was predicted by the online tool AlphaFold3, and the amino acid sequence of the marine antimicrobial peptide CD109 is shown in SEQ ID NO. 1. It shows that CD109 is a typical α-helical peptide, and since the C-terminal amidation modification does not change the spatial conformation of the polypeptide, the conformation of CD109C should also be α-helical. The antimicrobial peptide CD109C is an amphipathic α-helical cationic peptide.

[0035] The antimicrobial peptide CD109C in the present invention is synthesized by Sangon Biotech (Shanghai) Co., Ltd. through solid phase chemical synthesis, with a purity of more than 95%.

[0036] Example 2: Broad-spectrum antibacterial application of the marine antimicrobial peptide CD109 shown in SEQ ID NO.1.

[0037] 1. Determination of the antibacterial effect of marine antimicrobial peptide CD109 on various human pathogens Determination of the antibacterial effect of antimicrobial peptide CD109 on various human pathogens: Determination of minimum inhibitory concentration MIC: The seven human pathogens used in the experiment were purchased from Beina Chuanglian Biotechnology Co., Ltd., including Staphylococcus aureus 12600, Acinetobacter baumannii 19606, Pseudomonas aeruginosa PAO1 and Klebsiella pneumoniae.

[0038] The MIC of antimicrobial peptides was determined by the broth microdilution method, referring to the guidelines of the Clinical and Laboratory Standards Institute: Wayne, PA Performance Standards for Antimicrobial Disk Susceptibility Tests, Clinical and Laboratory Standards Institute, 1991.

[0039] The above pathogens were prepared according to the following method to obtain bacterial suspensions of each pathogen: the pathogens were inoculated into sterile LB liquid culture medium and cultured at 37°C overnight with shaking. The pathogens were inoculated into fresh LB liquid culture medium at a 1% inoculation rate and cultured until the exponential phase, and the bacterial concentration was adjusted to 1×10 5 cfu / mL to obtain bacterial solution. Then 180μL of bacterial solution was transferred to a 96-well plate. The antimicrobial peptide powder was dissolved in sterile water and diluted to a 2-fold antimicrobial peptide solution. The concentrations of the 2-fold antimicrobial peptide solution were 5μg / mL, 10μg / mL, 20μg / mL, 40μg / mL, 80μg / mL, 160μg / mL, 320μg / mL, 640μg / mL, 1280μg / mL and 2560μg / mL. 20μL of antimicrobial peptide solutions of different concentrations were added to the bacterial solution in the 96-well plate, respectively, so that the concentrations of antimicrobial peptides in the bacterial solution were 0.5μg / mL, 1μg / mL, 2μg / mL, 4μg / mL, 8μg / mL, 16μg / mL, 32μg / mL, 64μg / mL, 128μg / mL and 256μg / mL. After incubation at 37°C for 20 hours, the 96-well plate was tested for bacterial growth using an ELISA reader. MIC was defined as the minimum antimicrobial peptide concentration at which no bacterial growth was detected. Sterile water was used as the control group CK, and each group of experiments was repeated three times.

[0040] The minimum inhibitory concentration of antimicrobial peptide CD109 against Staphylococcus aureus 12600 was 2 μg / mL, the MIC against Acinetobacter baumannii 19606 was 32 μg / mL, and the MIC against Pseudomonas aeruginosa PAO1 and Klebsiella pneumoniae was 128 μg / mL.

[0041] Example 3: Broad-spectrum antibacterial application of the antimicrobial peptide CD109C shown in SEQ ID NO.2.

[0042] 1. Determination of the antibacterial effect of antimicrobial peptide CD109C on various human pathogens Determination of minimum inhibitory concentration MIC: The seven human pathogens used in the experiment were purchased from Beina Chuanglian Biotechnology Co., Ltd., including Staphylococcus aureus 12600, Staphylococcus aureus 33591, Staphylococcus aureus 33592, Acinetobacter baumannii 19606, Acinetobacter baumannii 53272, Pseudomonas aeruginosa PAO1 and Klebsiella pneumoniae.

[0043] The MIC of antimicrobial peptides was determined by the broth microdilution method, referring to the guidelines of the Clinical and Laboratory Standards Institute: Wayne, PA Performance Standards for Antimicrobial Disk Susceptibility Tests, Clinical and Laboratory Standards Institute, 1991.

[0044] The above pathogens were prepared according to the following method to obtain bacterial suspensions of each pathogen: the pathogens were inoculated into sterile LB liquid culture medium and cultured at 37°C overnight with shaking. The pathogens were inoculated into fresh LB liquid culture medium at a 1% inoculation rate and cultured until the exponential phase, and the bacterial concentration was adjusted to 1×10 5 cfu / mL to obtain bacterial solution. Then 180μL of bacterial solution was transferred to a 96-well plate. The antimicrobial peptide powder was dissolved in sterile water and diluted to a 2-fold antimicrobial peptide solution. The concentrations of the 2-fold antimicrobial peptide solution were 5μg / mL, 10μg / mL, 20μg / mL, 40μg / mL, 80μg / mL, 160μg / mL, 320μg / mL, 640μg / mL, 1280μg / mL and 2560μg / mL. 20μL of antimicrobial peptide solutions of different concentrations were added to the bacterial solution in the 96-well plate, respectively, so that the concentrations of antimicrobial peptides in the bacterial solution were 0.5μg / mL, 1μg / mL, 2μg / mL, 4μg / mL, 8μg / mL, 16μg / mL, 32μg / mL, 64μg / mL, 128μg / mL and 256μg / mL. After incubation at 37°C for 20 hours, the 96-well plate was tested for bacterial growth using an ELISA reader. MIC was defined as the minimum antimicrobial peptide concentration at which no bacterial growth was detected. Sterile water was used as the control group CK, and each group of experiments was repeated three times.

[0045] The results are as follows Figure 1As shown, the minimum inhibitory concentrations of antimicrobial peptide CD109C against Staphylococcus aureus 12600, Staphylococcus aureus 33591, and Staphylococcus aureus 33592 were 4 μg / mL, 8 μg / mL, and 16 μg / mL, respectively; the MICs against Acinetobacter baumannii 19606 and 53272 were 16 μg / mL and 8 μg / mL, respectively; the MICs against Pseudomonas aeruginosa PAO1 and Klebsiella pneumoniae were 16 μg / mL and 16 μg / mL, respectively.

[0046] 2. Determination of the bactericidal effect of antimicrobial peptide CD109C on Acinetobacter baumannii 19606 after treatment with different pH values As a therapeutic drug, the antimicrobial peptide CD109C needs to have good acid-base tolerance to cope with the different pH values ​​of different lesion sites. The present invention detected the MIC of the antimicrobial peptide CD109C against Acinetobacter baumannii 19606 after incubation for 1 hour under pH 2, pH 7.4, and pH 8.4. The specific steps are as follows: The PBS buffer was adjusted to pH 2, 7.4, and 8.4 with HCl and NaOH, respectively. The antimicrobial peptide powder was dissolved in the adjusted PBS buffer and diluted to prepare an antimicrobial peptide solution diluted 2 times in series. The concentrations of the solutions were 5 μg / mL, 10 μg / mL, 20 μg / mL, 40 μg / mL, 80 μg / mL, 160 μg / mL, 320 μg / mL, 640 μg / mL, 1280 μg / mL, and 2560 μg / mL, respectively. The solutions were incubated at 37°C for 1 hour, and then the MIC values ​​against Acinetobacter baumannii 19606 were detected.

[0047] The results are as follows Figure 2 As shown, the MIC of CD109C against Acinetobacter baumannii 19606 remained at 16 μg / mL after treatment with three pH values. Three replicates were set for each group of experiments.

[0048] 3. Cytotoxicity assay of antimicrobial peptide CD109C The cytotoxicity experiment of antimicrobial peptide CD109C was carried out using human skin keratinocytes HaCat and bronchial epithelial cells BEAS-2B.

[0049] The above cells were inoculated in high-glucose DMEM complete medium containing 10% fetal bovine serum. The high-glucose DMEM complete medium containing 10% fetal bovine serum also contains 10000 U / mL penicillin and 10000μg / mL streptomycin, referred to as complete medium. Place in a cell culture incubator at 37°C, 5% CO2, observe the cell status every day and change the medium in time. When changing the medium, discard the old medium first, wash three times with 37°C PBS, and then add fresh complete culture medium. Culture to the logarithmic phase.

[0050] Take the cells in logarithmic phase and discard the culture supernatant. Wash with PBS and digest with 0.25% trypsin for 3 min. Use complete culture medium to terminate digestion and centrifuge at room temperature at 800 rpm for 5 min. Discard the supernatant and pipette the cells with 1 mL complete culture medium to prepare a cell suspension and count. Dilute the cell suspension to 158,000 cells / mL according to the counting results and inoculate into a 96-well plate, 100 μL per well, i.e. 15,800 cells / well, and culture overnight in a 37°C incubator.

[0051] Complete medium was used to dissolve and dilute the antimicrobial peptide CD109C to form 350 μL of antimicrobial peptide working solutions with concentrations of 128 μg / mL, 96 μg / mL, and 64 μg / mL. The culture medium was removed from the cells after overnight culture, and 100 μL of antimicrobial peptide working solutions of different concentrations were added to the experimental group, and 100 μL of complete medium was added to the control group. The blank was the complete medium without inoculated cells. Three replicates were set for each concentration and cultured in a 37°C incubator for 24 h.

[0052] After 24 h of drug administration and culture, MTT reagent was added and incubated in a 37°C incubator for 4 h. The supernatant was carefully aspirated, 100 μL DMSO was added to the wells and shaken, and the plate was read at a wavelength of 570 nm on a microplate reader.

[0053] After testing, the cytotoxicity results of the antimicrobial peptide CD109C were as follows Figure 3 As shown, when the treatment concentration of the antimicrobial peptide CD109C reached 128 μg / mL, the survival rates of skin keratinocytes HaCat and bronchial epithelial cells BEAS-2B were 98.03% and 94.4%, respectively. Its extremely low cytotoxicity gives it excellent medical therapeutic potential.

[0054] In summary, the antimicrobial peptide CD109C prepared by the present invention can effectively inhibit multiple drug-resistant human pathogens, and the minimum inhibitory concentrations of Staphylococcus aureus 12600, Staphylococcus aureus 33591, and Staphylococcus aureus 33592 are 4 μg / mL, 8 μg / mL, and 16 μg / mL, respectively, and the MICs of Acinetobacter baumannii 19606 and Acinetobacter baumannii 53272 are 16 μg / mL and 8 μg / mL, respectively, and the MICs of Pseudomonas aeruginosa PAO1 and Klebsiella pneumoniae are 16 μg / mL and 16 μg / mL, respectively. CD109C has good pH stability, and after incubation for 1 hour under pH2, pH7.4, and pH8.4 conditions, the MIC of Acinetobacter baumannii 19606 remains at 16 μg / mL. CD109C has extremely low cytotoxicity. Skin keratinocytes HaCat and bronchial epithelial cells BEAS-2B still maintained 98.02% and 94.4% survival rates after being treated with 128 μg / mL CD109C for 24 hours. The antimicrobial peptide CD109C shows extremely high antibacterial value as a medical drug and can provide an alternative medicinal resource for future clinical use against multiple drug-resistant pathogens.

[0055] Although the preferred embodiments of the present invention have been described, those skilled in the art may make other changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0056] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A marine antimicrobial peptide CD109, characterized in that: The amino acid sequence of the marine antimicrobial peptide CD109 is shown in SEQ ID NO.1: MWKLPKWRNGRRRGFKIPRW.

2. An antimicrobial peptide CD109C, characterized in that: The antimicrobial peptide CD109C is obtained by modifying the marine antimicrobial peptide CD109 according to claim 1 through C-terminal amidation. The amino acid sequence of the antimicrobial peptide CD109C is: MWKLPKWRNGRRRGFKIPRW-NH2. The molecular formula of the antimicrobial peptide is C 125 H 195 N 43 O 21 S.

3. Use of the marine antimicrobial peptide CD109 according to claim 1 or the antimicrobial peptide CD109C according to claim 2 in the preparation of an antimicrobial product, characterized in that: The antibacterial product is used to inhibit Staphylococcus aureus, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae.

4. The use according to claim 3, characterized in that: The antibacterial product is a medicine or an antibacterial agent.

5. The use according to claim 4, characterized in that: The antibacterial product uses marine antibacterial peptide CD109 or antibacterial peptide CD109C as the only active ingredient.

6. The use according to claim 3, characterized in that: The minimum inhibitory concentration of the marine antimicrobial peptide CD109 against Staphylococcus aureus is 2 μg / mL, the minimum inhibitory concentration against Acinetobacter baumannii is 32 μg / mL, the minimum inhibitory concentration against Pseudomonas aeruginosa is 128 μg / mL, and the minimum inhibitory concentration against Klebsiella pneumoniae is 128 μg / mL.

7. The use according to claim 3, characterized in that: The minimum inhibitory concentration of the antimicrobial peptide CD109C against Staphylococcus aureus is 4 μg / mL, the minimum inhibitory concentration against Acinetobacter baumannii is 8 μg / mL, the minimum inhibitory concentration against Pseudomonas aeruginosa is 16 μg / mL, and the minimum inhibitory concentration against Klebsiella pneumoniae is 16 μg / mL.

8. The use according to claim 4, characterized in that: The antibacterial agent is obtained by dissolving marine antimicrobial peptide CD109 or antimicrobial peptide CD109C in sterile water.

9. The use according to claim 8, characterized in that: The concentration of the antimicrobial peptide in the antibacterial agent is 2 μg / mL to 128 μg / mL.

10. The use according to claim 4, characterized in that: The drug also includes pharmaceutically acceptable excipients.

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