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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:Superoxide dismutase activity confers (p)ppGpp-mediated antibiotic tolerance to stationary-phase Pseudomonas aeruginosa.
Authors:Martins D,  McKay G,  Sampathkumar G,  Khakimova M,  English AM,  Nguyen D
Link:https://www.ncbi.nlm.nih.gov/pubmed/30201715?dopt=Abstract
Category:Proc Natl Acad Sci U S A
PMID:30201715
Dept Affiliation: CHEMBIOCHEM
1 Department of Microbiology and Immunology, McGill University, Montreal, QC H3A OG4, Canada.
2 Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
3 Department of Chemistry and Biochemistry, Concordia University, Montreal, QC H3G 1M8, Canada.
4 Department of Microbiology and Immunology, McGill University, Montreal, QC H3A OG4, Canada; dao.nguyen@mcgill.ca.
5 Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada.

Description:

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

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

Abstract

Metabolically quiescent bacteria represent a large proportion of those in natural and host environments, and they are often refractory to antibiotic treatment. Such drug tolerance is also observed in the laboratory during stationary phase, when bacteria face stress and starvation-induced growth arrest. Tolerance requires (p)ppGpp signaling, which mediates the stress and starvation stringent response (SR), but the downstream effectors that confer tolerance are unclear. We previously demonstrated that the SR is linked to increased antioxidant defenses in Pseudomonas aeruginosa We now demonstrate that superoxide dismutase (SOD) activity is a key factor in SR-mediated multidrug tolerance in stationary-phase P. aeruginosa Inactivation of the SR leads to loss of SOD activity and decreased multidrug tolerance during stationary phase. Genetic or chemical complementation of SOD activity of the ?relA spoT mutant (?SR) is sufficient to restore antibiotic tolerance to WT levels. Remarkably, we observe high membrane permeability and increased drug internalization upon ablation of SOD activity. Combined, our results highlight an unprecedented mode of SR-mediated multidrug tolerance in stationary-phase P. aeruginosa and suggest that inhibition of SOD activity may potentiate current antibiotics.

PMID: 30201715 [PubMed - indexed for MEDLINE]