Wu Xiaozhe, Li Zhan, Li Xiaolu, Tian Yaomei, Fan Yingzi, Yu Chaoheng, Zhou Bailing, Liu Yi, Xiang Rong, Yang Li
State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University.
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.
Drug Des Devel Ther. 2017 Mar 22;11:939-946. doi: 10.2147/DDDT.S107195. eCollection 2017.
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.
抗生素耐药菌对公众健康构成了巨大威胁。在本研究中，研究了抗菌肽（AMPs）与抗生素对几种多重耐药菌株的协同作用，并分析了它们对阿奇霉素（AZT）耐药基因的协同作用，以确定耐药性与这些协同作用之间的关系。采用棋盘法评估了AMPs（DP7和CLS001）与几种抗生素（庆大霉素、万古霉素[VAN]、AZT和阿莫西林）对临床菌株（和）的协同作用。使用定量聚合酶链反应在耐药菌株中鉴定出AZT耐药基因（、和）。对于所有测试的对不同抗生素耐药的临床分离株，DP7具有较高的抗菌活性（≤32 mg/L）。当DP7与VAN或AZT联合使用时，效果最常表现为协同作用。当我们研究AZT耐药分离株的耐药基因时，DP7-AZT的协同作用最常发生在高耐药菌株或携带两个以上AZT耐药基因的菌株中。对受DP7-AZT协同影响的菌株进行透射电子显微镜分析，未发现明显的形态学变化，这表明分子水平的机制在DP7-AZT的协同作用中起重要作用。AMPs DP7加抗生素AZT或VAN更有效，尤其是对高度耐药菌株。
