Abstract：
In recent years, new evidence has shown that the SOS response plays an important role in the response to antimicrobials, with involvement in the generation of clinical resistance. Here we evaluate the impact of heterogeneous expression of the SOS response in clinical isolates of Escherichia coli on response to the fluoroquinolone, ciprofloxacin. In silico analysis of whole genome sequencing data showed remarkable sequence conservation of the SOS response regulators, RecA and LexA. Despite the genetic homogeneity, our results revealed a marked differential heterogeneity in SOS response activation, both at population and single-cell level, among clinical isolates of E. coli in the presence of subinhibitory concentrations of ciprofloxacin. Four main stages of SOS response activation were identified and correlated with cell filamentation. Interestingly, there was a correlation between clinical isolates with higher expression of the SOS response and further progression to resistance. This heterogeneity in response to DNA damage repair (mediated by the SOS response) and induced by antimicrobial agents could be a new factor with implications for bacterial evolution and survival contributing to the generation of antimicrobial resistance.
摘要：
近年来,新的证据表明，SOS反应在抗微生物药物的反应中起着重要作用，参与临床耐药性的产生。在这里，我们评估了在大肠杆菌临床分离株中SOS反应的异质表达对氟喹诺酮反应的影响，环丙沙星.全基因组测序数据的计算机模拟分析显示，SOS反应调节因子具有显著的序列保守性，RecA和LexA.尽管遗传同质性，我们的结果揭示了SOS反应激活的显著差异异质性，在群体和单细胞水平上，在存在亚抑制浓度的环丙沙星的大肠杆菌临床分离株中。确定了SOS反应激活的四个主要阶段，并与细胞成丝相关。有趣的是,SOS应答表达较高的临床分离株与进一步进展为耐药之间存在相关性.响应DNA损伤修复（由SOS反应介导）并由抗微生物剂诱导的这种异质性可能是对细菌进化和存活具有影响的新因素，有助于产生抗微生物耐药性。
