Oxidative stress antagonizes fluoroquinolone drug sensitivity via the SoxR-SUF Fe-S cluster homeostatic axis.
Anti-Bacterial Agents
/ pharmacology
Bacterial Proteins
/ metabolism
Carrier Proteins
/ genetics
Drug Antagonism
Drug Resistance, Bacterial
/ drug effects
Escherichia coli
/ drug effects
Escherichia coli Infections
/ drug therapy
Escherichia coli Proteins
/ genetics
Gene Expression Regulation, Bacterial
Humans
Iron-Sulfur Proteins
/ metabolism
Methylphenazonium Methosulfate
/ pharmacology
Microbial Sensitivity Tests
Norfloxacin
/ pharmacology
Oxidative Stress
/ drug effects
Transcription Factors
/ metabolism
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
26
05
2020
accepted:
15
10
2020
revised:
17
11
2020
pubmed:
3
11
2020
medline:
8
1
2021
entrez:
2
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33137124
doi: 10.1371/journal.pgen.1009198
pii: PGENETICS-D-20-00845
pmc: PMC7671543
doi:
Substances chimiques
AcrAB-TolC protein, E coli
0
Anti-Bacterial Agents
0
Bacterial Proteins
0
Carrier Proteins
0
Escherichia coli Proteins
0
Iron-Sulfur Proteins
0
Transcription Factors
0
SoxR protein, Bacteria
137804-81-0
Methylphenazonium Methosulfate
299-11-6
Norfloxacin
N0F8P22L1P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009198Déclaration de conflit d'intérêts
no authors have competing interests.
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