Total Alkaloids of Sophorea alopecuroides‐induced Down‐regulation of AcrAB‐ToLC Efflux Pump Reverses Susceptibility to Ciprofloxacin in Clinical Multidrug Resistant Escherichia coli isolates
Total Alkaloids of Sophorea alopecuroides‐induced Down‐regulation of AcrAB‐ToLC Efflux Pump Reverses Susceptibility to Ciprofloxacin in Clinical Multidrug Resistant Escherichia coli isolates
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DOI：
10.1002/ptr.4623
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发表时间：
2012-11
影响因子：
7.2
通讯作者：
Xuezhang Zhou;Fang Jia;Xiaoming Liu;Yujiong Wang
中科院分区：
文献类型：
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作者：
Xuezhang Zhou;Fang Jia;Xiaoming Liu;Yujiong Wang
本文报道了苦豆总生物碱（TASA）对氨苄西林（AM）、阿米卡星（AN）、头孢噻肟（CTX）和环丙沙星（CIP）4种抗生素耐药大肠埃希菌的抑制作用。TASA对多药耐药（MDR）菌株具有抗菌活性。与TASA组合，观察到测试的抗生素对MRD分离株的协同作用。同样，通过微量肉汤稀释棋盘法测定，用较低剂量TASA预处理的分离株对CIP的亲和性增加了16-32倍。此外，定量逆转录-聚合酶链反应（qRT-PCR）分析显示，供试MDR分离株中AcrAB-TolC泵系统存在组成性过表达。用TASA预处理MDR分离株导致acrA和acrB基因表达在统计学上下调，acrR基因表达上调（p 0.05）。这些结果表明，TASA诱导的CIP逆转耐药可能部分通过抑制这些分离株中AcrAB‐TolC泵活性的机制，这意味着TASA可用作开发针对AcrAB‐TolC泵介导的大肠杆菌MDR的外排泵抑制剂（EPI）的潜在天然来源。大肠杆菌分离株。版权所有© 2012约翰威利父子有限公司.
In this report, total alkaloids extracted from the seeds of Sophorea alopecuroides (TASA) was evaluated against clinical Escherichia coli isolates resistant to four tested antibiotics, ampicillin (AM), amikacin (AN), cefotaxime (CTX) and ciprofloxacin (CIP). The TASA showed an antibacterial activity against the multidrug resistant (MDR) isolates. In combination with TASA, synergistic effects on the tested antibiotics against the MRD isolates were observed. Similarly, the isolates pretreated with a lower dose of TASA yielded increased and stable susceptibilities to CIP by 16–32‐fold determined by a microbroth dilution checkerboard method. Moreover, quantitative reverse transcription–polymerase chain reaction (qRT‐PCR) analysis revealed a constitutive overexpression of the AcrAB‐TolC pump system in the tested MDR isolates. The pretreatment of MDR isolates with TASA resulted in a statistically down‐regulated expression of acrA and acrB genes, and an up‐regulated expression of acrR gene (p 0.05). These results suggested that the TASA‐induced reversal resistance to CIP might be partially through a mechanism of inhibition of the AcrAB‐TolC pump activity in these isolates, implying that the TASA can be used as a potential natural source to develop efflux pump inhibitors (EPI) against AcrAB‐TolC pump mediated MDR in E. coli isolates. Copyright © 2012 John Wiley & Sons, Ltd.