title: Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria.
abstract: 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 (Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, andEscherichia coli). The AZT-resistance genes (ermA, ermB, ermC, mefA, andmsrA) 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 theS. aureusstrain 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.
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University.
authors.forename: Xiaozhe
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Li
authors.affiliation: International Center for Translational Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu; Department of Plastic and Burn Surgery, Affiliated Hospital of Southwest Medical University, Luzhou.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University.
authors.forename: Yaomei
authors.initials: Y
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University.
authors.forename: Chaoheng
authors.initials: C
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University.
authors.forename: Bailing
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Microbial Examination, Sichuan Center for Disease Control and Prevention, Chengdu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Nankai University School of Medicine, Tianjin, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides
keywords: antimicrobial peptide; drug synergy; resistant bacteria