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Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens

With the increasing bacterial resistance to traditional antibiotics, there is an urgent need for the development of alternative drugs or adjuvants of antibiotics to enhance antibacterial efficiency. The combination of antimicrobial peptides (AMPs) and traditional antibiotics is a potential alternati...

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Autores principales: Lu, Yi, Tian, Hongliang, Chen, Runqiu, Liu, Qian, Jia, Kaixiang, Hu, Dong-Liang, Chen, Hongwei, Ye, Chao, Peng, Lianci, Fang, Rendong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335283/
https://www.ncbi.nlm.nih.gov/pubmed/35910608
http://dx.doi.org/10.3389/fmicb.2022.953720
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author Lu, Yi
Tian, Hongliang
Chen, Runqiu
Liu, Qian
Jia, Kaixiang
Hu, Dong-Liang
Chen, Hongwei
Ye, Chao
Peng, Lianci
Fang, Rendong
author_facet Lu, Yi
Tian, Hongliang
Chen, Runqiu
Liu, Qian
Jia, Kaixiang
Hu, Dong-Liang
Chen, Hongwei
Ye, Chao
Peng, Lianci
Fang, Rendong
author_sort Lu, Yi
collection PubMed
description With the increasing bacterial resistance to traditional antibiotics, there is an urgent need for the development of alternative drugs or adjuvants of antibiotics to enhance antibacterial efficiency. The combination of antimicrobial peptides (AMPs) and traditional antibiotics is a potential alternative to enhance antibacterial efficiency. In this study, we investigated the synergistic bactericidal effect of AMPs, including chicken (CATH-1,−2,−3, and -B1), mice (CRAMP), and porcine (PMAP-36 and PR-39) in combination with conventional antibiotics containing ampicillin, tetracycline, gentamicin, and erythromycin against Staphylococcus aureus, Salmonella enteritidis, and Escherichia coli. The results showed that the minimum bactericidal concentration (MBC) of CATH-1,−3 and PMAP-36 was lower than 10 μM, indicating that these three AMPs had good bacterial activity against S. aureus, S. enteritidis, and E. coli. Then, the synergistic antibacterial activity of AMPs and antibiotics combination was determined by the fractional bactericidal concentration index (FBCI). The results showed that the FBCI of AMPs (CATH-1,−3 and PMAP-36) and erythromycin was lower than 0.5 against bacterial pathogens, demonstrating that they had a synergistic bactericidal effect. Furthermore, the time-killing kinetics of AMPs (CATH-1,−3 and PMAP-36) in combination with erythromycin showed that they had a continuous killing effect on bacteria within 3 h. Notably, the combination showed lower hemolytic activity and cytotoxicity to mammal cells compared to erythromycin and peptide alone treatment. In addition, the antibacterial mechanism of CATH-1 and erythromycin combination against E. coli was studied. The results of the scanning electron microscope showed that CATH-1 enhanced the antibacterial activity of erythromycin by increasing the permeability of bacterial cell membrane. Moreover, the results of bacterial migration movement showed that the combination of CATH-1 and erythromycin significantly inhibits the migration of E. coli. Finally, drug resistance analysis was performed and the results showed that CATH-1 delayed the emergence of E. coli resistance to erythromycin. In conclusion, the combination of CATH-1 and erythromycin has synergistic antibacterial activity and reduces the emergence of bacterial drug resistance. Our study provides valuable information to develop AMPs as potential substitutes or adjuvants for traditional antibiotics.
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spelling pubmed-93352832022-07-30 Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens Lu, Yi Tian, Hongliang Chen, Runqiu Liu, Qian Jia, Kaixiang Hu, Dong-Liang Chen, Hongwei Ye, Chao Peng, Lianci Fang, Rendong Front Microbiol Microbiology With the increasing bacterial resistance to traditional antibiotics, there is an urgent need for the development of alternative drugs or adjuvants of antibiotics to enhance antibacterial efficiency. The combination of antimicrobial peptides (AMPs) and traditional antibiotics is a potential alternative to enhance antibacterial efficiency. In this study, we investigated the synergistic bactericidal effect of AMPs, including chicken (CATH-1,−2,−3, and -B1), mice (CRAMP), and porcine (PMAP-36 and PR-39) in combination with conventional antibiotics containing ampicillin, tetracycline, gentamicin, and erythromycin against Staphylococcus aureus, Salmonella enteritidis, and Escherichia coli. The results showed that the minimum bactericidal concentration (MBC) of CATH-1,−3 and PMAP-36 was lower than 10 μM, indicating that these three AMPs had good bacterial activity against S. aureus, S. enteritidis, and E. coli. Then, the synergistic antibacterial activity of AMPs and antibiotics combination was determined by the fractional bactericidal concentration index (FBCI). The results showed that the FBCI of AMPs (CATH-1,−3 and PMAP-36) and erythromycin was lower than 0.5 against bacterial pathogens, demonstrating that they had a synergistic bactericidal effect. Furthermore, the time-killing kinetics of AMPs (CATH-1,−3 and PMAP-36) in combination with erythromycin showed that they had a continuous killing effect on bacteria within 3 h. Notably, the combination showed lower hemolytic activity and cytotoxicity to mammal cells compared to erythromycin and peptide alone treatment. In addition, the antibacterial mechanism of CATH-1 and erythromycin combination against E. coli was studied. The results of the scanning electron microscope showed that CATH-1 enhanced the antibacterial activity of erythromycin by increasing the permeability of bacterial cell membrane. Moreover, the results of bacterial migration movement showed that the combination of CATH-1 and erythromycin significantly inhibits the migration of E. coli. Finally, drug resistance analysis was performed and the results showed that CATH-1 delayed the emergence of E. coli resistance to erythromycin. In conclusion, the combination of CATH-1 and erythromycin has synergistic antibacterial activity and reduces the emergence of bacterial drug resistance. Our study provides valuable information to develop AMPs as potential substitutes or adjuvants for traditional antibiotics. Frontiers Media S.A. 2022-07-15 /pmc/articles/PMC9335283/ /pubmed/35910608 http://dx.doi.org/10.3389/fmicb.2022.953720 Text en Copyright © 2022 Lu, Tian, Chen, Liu, Jia, Hu, Chen, Ye, Peng and Fang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Lu, Yi
Tian, Hongliang
Chen, Runqiu
Liu, Qian
Jia, Kaixiang
Hu, Dong-Liang
Chen, Hongwei
Ye, Chao
Peng, Lianci
Fang, Rendong
Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens
title Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens
title_full Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens
title_fullStr Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens
title_full_unstemmed Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens
title_short Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens
title_sort synergistic antimicrobial effect of antimicrobial peptides cath-1, cath-3, and pmap-36 with erythromycin against bacterial pathogens
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335283/
https://www.ncbi.nlm.nih.gov/pubmed/35910608
http://dx.doi.org/10.3389/fmicb.2022.953720
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