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

Abstract : 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.
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https://hal-amu.archives-ouvertes.fr/hal-02995849
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Submitted on : Friday, November 27, 2020 - 10:31:11 AM
Last modification on : Tuesday, October 19, 2021 - 10:58:57 PM
Long-term archiving on: : Sunday, February 28, 2021 - 6:53:10 PM

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Audrey Gerstel, Jordi Zamarreño Beas, Yohann Duverger, Emmanuelle Bouveret, Frédéric Barras, et al.. Oxidative stress antagonizes fluoroquinolone drug sensitivity via the SoxR-SUF Fe-S cluster homeostatic axis. PLoS Genetics, Public Library of Science, 2020, 16 (11), pp.e1009198. ⟨10.1371/journal.pgen.1009198⟩. ⟨hal-02995849⟩

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