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Sublethal Paraquat Confers Multidrug Tolerance in Pseudomonas aeruginosa by Inducing Superoxide Dismutase Activity and Lowering Envelope Permeability.

Author(s): Martins D, McKay GA, English AM, Nguyen D

Stressors and environmental cues shape the physiological state of bacteria, and thus how they subsequently respond to antibiotic toxicity. To understand how superoxide stress can modulate survival to bactericidal antibiotics, we examined the effect of intra...

Article GUID: 33101252
Ctt1 catalase activity potentiates antifungal azoles in the emerging opportunistic pathogen Saccharomyces cerevisiae.

Author(s): Martins D, Nguyen D, English AM

Sci Rep. 2019 Jun 24;9(1):9185 Authors: Martins D, Nguyen D, English AM

Article GUID: 31235707
Superoxide dismutase activity confers (p)ppGpp-mediated antibiotic tolerance to stationary-phase Pseudomonas aeruginosa.

Author(s): Martins D, McKay G, Sampathkumar G, Khakimova M, English AM, Nguyen D

Proc Natl Acad Sci U S A. 2018 09 25;115(39):9797-9802 Authors: Martins D, McKay G, Sampathkumar G, Khakimova M, English AM, Nguyen D

Article GUID: 30201715
Title:Sublethal Paraquat Confers Multidrug Tolerance in Pseudomonas aeruginosa by Inducing Superoxide Dismutase Activity and Lowering Envelope Permeability.
Authors:Martins D,  McKay GA,  English AM,  Nguyen D
Link:https://www.ncbi.nlm.nih.gov/pubmed/33101252
DOI:10.3389/fmicb.2020.576708
Category:Front Microbiol
PMID:33101252
Dept Affiliation: CHEMBIOCHEM
1 Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
2 Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
3 Department of Chemistry and Biochemistry, Concordia University, Montreal, QC, Canada.
4 Department of Medicine, McGill University, Montreal, QC, Canada.

Description:

Sublethal Paraquat Confers Multidrug Tolerance in Pseudomonas aeruginosa by Inducing Superoxide Dismutase Activity and Lowering Envelope Permeability.

Front Microbiol. 2020; 11:576708

Authors: Martins D, McKay GA, English AM, Nguyen D

Abstract

Stressors and environmental cues shape the physiological state of bacteria, and thus how they subsequently respond to antibiotic toxicity. To understand how superoxide stress can modulate survival to bactericidal antibiotics, we examined the effect of intracellular superoxide generators, paraquat and menadione, on stationary-phase antibiotic tolerance of the opportunistic pathogen, Pseudomonas aeruginosa. We tested how pre-challenge with sublethal paraquat and menadione alters the tolerance to ofloxacin and meropenem in wild-type P. aeruginosa and mutants lacking superoxide dismutase (SOD) activity (sodAB), the paraquat responsive regulator soxR, (p)ppGpp signaling (relA spoT mutant), or the alternative sigma factor rpoS. We confirmed that loss of SOD activity impairs ofloxacin and meropenem tolerance in stationary phase cells, and found that sublethal superoxide generators induce drug tolerance by stimulating SOD activity. This response is rapid, requires de novo protein synthesis, and is RpoS-dependent but does not require (p)ppGpp signaling nor SoxR. We further showed that pre-challenge with sublethal paraquat induces a SOD-dependent reduction in cell-envelope permeability and ofloxacin penetration. Our results highlight a novel mechanism of hormetic protection by superoxide generators, which may have important implications for stress-induced antibiotic tolerance in P. aeruginosa cells.

PMID: 33101252 [PubMed]