Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria

• Published in: Drug design, development and therapy development and therapy, 2017-01, Vol.11, p.939-946
• Main Authors: Wu, Xiaozhe, Li, Zhan, Li, Xiaolu, Tian, Yaomei, Fan, Yingzi, Yu, Chaoheng, Zhou, Bailing, Liu, Yi, Xiang, Rong, Yang, Li
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii - drug effects; Amoxicillin; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; antimicrobial peptide; Antimicrobial peptides; Antimicrobial resistance; Azithromycin; Bacteria; Clinical isolates; Deoxyribonucleic acid; Disease control; DNA; Dose-Response Relationship, Drug; Drug resistance; Drug Resistance, Multiple, Bacterial - drug effects; Drug Synergism; drug synergy; E coli; Escherichia coli - drug effects; Gene expression; Genes; Genetic testing; Gentamicin; Health aspects; Health risks; Hospitals; Laboratories; Microbial drug resistance; Microbial Sensitivity Tests; Microscopic analysis; Multidrug resistance; Multidrug resistant organisms; Original Research; Penicillin; Peptides; Pharmaceuticals; Polymerase chain reaction; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Public health; resistant bacteria; Staphylococcus aureus - drug effects; Strains (organisms); Structure-Activity Relationship; Synergistic effect; Testing; Transmission electron microscopy; Vancomycin; Zidovudine
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S107195

Antibiotic-resistant bacteria present a great threat to public health. In this study, the synergistic effects of antimicrobial peptides (AMPs) and antibiotics on several multidrug-resistant bacterial strains were studied, and their synergistic effects on azithromycin (AZT)-resistance genes were analyzed to determine the relationships between antimicrobial resistance and these synergistic effects. A checkerboard method was used to evaluate the synergistic effects of AMPs (DP7 and CLS001) and several antibiotics (gentamicin, vancomycin [VAN], AZT, and amoxicillin) on clinical bacterial strains ( , and ). The AZT-resistance genes ( , and ) were identified in the resistant strains using quantitative polymerase chain reaction. For all the clinical isolates tested that were resistant to different antibiotics, DP7 had high antimicrobial activity (≤32 mg/L). When DP7 was combined with VAN or AZT, the effect was most frequently synergistic. When we studied the resistance genes of the AZT-resistant isolates, the synergistic effect of DP7-AZT occurred most frequently in highly resistant strains or strains carrying more than two AZT-resistance genes. A transmission electron microscopic analysis of the strain synergistically affected by DP7-AZT showed no noteworthy morphological changes, suggesting that a molecular-level mechanism plays an important role in the synergistic action of DP7-AZT. AMP DP7 plus the antibiotic AZT or VAN is more effective, especially against highly antibiotic-resistant strains.