Oxidative stress antagonizes fluoroquinolone drug sensitivity via the SoxR-SUF Fe-S cluster homeostatic axis

English version

Autoři: Audrey Gerstel ^aff001; Jordi Zamarreño Beas ^aff001; Yohann Duverger ^aff001; Emmanuelle Bouveret ^aff002; Frédéric Barras ^aff001; Béatrice Py ^aff001
Působiště autorů: Laboratoire de Chimie Bactérienne, Institut de Microbiologie de la Méditerranée, Aix-Marseille Université, Marseille, France ^aff001; Laboratoire de Chimie Bactérienne, Aix-Marseille Université-CNRS UMR7283, Institut de Microbiologie de la Méditerranée, Marseille, France ^aff001; SAMe Unit, Département de Microbiologie, Institut Pasteur, CNRS UMR IMM 2001, Paris, France ^aff002
Vyšlo v časopise: Oxidative stress antagonizes fluoroquinolone drug sensitivity via the SoxR-SUF Fe-S cluster homeostatic axis. PLoS Genet 16(11): e1009198. doi:10.1371/journal.pgen.1009198
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009198

Souhrn

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.

Klíčová slova:

Antibiotic resistance – Antibiotics – Biosynthesis – DNA transcription – Homeostasis – Operons – Oxidative stress – Plasmid construction

Zdroje

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