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Heterogeneity of SOS response expression in clinical isolates of Escherichia coli influences adaptation to antimicrobial stress
Drug Resistance Updates ( IF 15.8 ) Pub Date : 2024-04-23 , DOI: 10.1016/j.drup.2024.101087
Sara Diaz-Diaz 1 , Andrea Garcia-Montaner 2 , Roberta Vanni 2 , Marina Murillo-Torres 3 , Esther Recacha 4 , Marina R Pulido 5 , Maria Romero-Muñoz 2 , Fernando Docobo-Pérez 5 , Alvaro Pascual 6 , Jose Manuel Rodriguez-Martinez 5
Affiliation  

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 on response to the fluoroquinolone, ciprofloxacin. 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 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.

中文翻译:


大肠杆菌临床分离株中 SOS 反应表达的异质性影响对抗菌应激的适应



近年来,新的证据表明,SOS 反应在抗菌药物的反应中发挥着重要作用,参与临床耐药性的产生。在这里,我们评估了临床分离株中 SOS 反应的异质表达对氟喹诺酮、环丙沙星反应的影响。全基因组测序数据分析显示 SOS 反应调节因子 RecA 和 LexA 具有显着的序列保守性。尽管存在遗传同质性,但我们的结果揭示了在存在亚抑制浓度环丙沙星的临床分离株中,SOS反应激活在群体和单细胞水平上存在显着的差异异质性。确定了 SOS 反应激活的四个主要阶段并与细胞丝状化相关。有趣的是,SOS 反应表达较高的临床分离株与进一步进展为耐药性之间存在相关性。这种对 DNA 损伤修复(由 SOS 反应介导)和抗菌药物诱导的异质性可能是一个新因素,对细菌进化和生存产生影响,从而导致抗菌药物耐药性的产生。
更新日期:2024-04-23
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