期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 66, 期 9, 页码 2057-2060出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkr258
关键词
multidrug efflux; AcrAB-TolC; SSRIs; sertraline; NR; substrate binding pocket
资金
- Medical Faculty of Albert-Ludwigs-University (Freiburg, Germany)
Objectives: To evaluate the antimicrobial and synergistic (hypothetically due to the inhibition of efflux pumps) effects of selective serotonin reuptake inhibitors (SSRIs) in Escherichia coli strains overproducing various resistance-nodulation-division (RND) efflux pumps. Methods: MICs of various SSRIs and of clinically relevant antibiotics in the presence and absence of sertraline were determined for E. coli strains overproducing the RND efflux pumps AcrAB, AcrEF, MdtEF and MexAB. The effect of sertraline on Nile red efflux was evaluated in a real-time efflux assay. Expression of marA and acrB was monitored using quantitative RT-PCR. Results: In MIC assays there was limited synergy of sertraline with tetracycline, oxacillin, linezolid and clarithromycin, depending on the individual pump overexpressed and on whether rich or minimal medium was used. Sertraline, as the most potent SSRI with regard to bacterial growth inhibition, led to rapid dose-dependent Nile red efflux inhibition, and was also found to increase the expression of marA and acrB. Conclusions: A possible explanation for the discrepancy between the MIC and real-time efflux assays was that sertraline is a weak inducer of marA and acrB, thereby reducing its initial antibacterial and sensitizing effects over time. The results indicate that sertraline may be useful as a model efflux pump inhibitor for in vitro short-term experiments in E. coli, but is unlikely to be clinically useful as a co-drug against Gram-negative
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据