Laboratoire de Chimie Bactérienne, Aix-Marseille Université-CNRS UMR7283, Institut de Microbiologie de la Méditerranée, Marseille, France.
SAMe Unit, Département de Microbiologie, Institut Pasteur, CNRS UMR IMM 2001, Paris, France.
PLoS Genet. 2020 Nov 2;16(11):e1009198. doi: 10.1371/journal.pgen.1009198. eCollection 2020 Nov.
The level of antibiotic resistance exhibited by bacteria can vary as a function of environmental conditions. Here, we report that phenazine-methosulfate (PMS), a redox-cycling compound (RCC) enhances resistance to fluoroquinolone (FQ) norfloxacin. Genetic analysis showed that E. coli adapts to PMS stress by making Fe-S clusters with the SUF machinery instead of the ISC one. Based upon phenotypic analysis of soxR, acrA, and micF mutants, we showed that PMS antagonizes fluoroquinolone toxicity by SoxR-mediated up-regulation of the AcrAB drug efflux pump. Subsequently, we showed that despite the fact that SoxR could receive its cluster from either ISC or SUF, only SUF is able to sustain efficient SoxR maturation under exposure to prolonged PMS period or high PMS concentrations. This study furthers the idea that Fe-S cluster homeostasis acts as a sensor of environmental conditions, and because its broad influence on cell metabolism, modifies the antibiotic resistance profile of E. coli.
细菌表现出的抗生素耐药水平可以作为环境条件的函数而变化。在这里，我们报告说，吩嗪-甲磺酸盐（PMS），一种氧化还原循环化合物（RCC），增强了对氟喹诺酮（FQ）诺氟沙星的耐药性。遗传分析表明，大肠杆菌通过 SUF 机制而不是 ISC 机制制造 Fe-S 簇来适应 PMS 应激。基于 soxR、acrA 和 micF 突变体的表型分析，我们表明 PMS 通过 SoxR 介导的上调 AcrAB 药物外排泵来拮抗氟喹诺酮毒性。随后，我们表明，尽管 SoxR 可以从 ISC 或 SUF 获得其簇，但只有 SUF 能够在长时间暴露于 PMS 或高 PMS 浓度下维持有效的 SoxR 成熟。这项研究进一步说明了铁硫簇动态平衡作为环境条件的传感器的作用，并且由于其对细胞代谢的广泛影响，改变了大肠杆菌的抗生素耐药谱。
