Magnesium homeostasis protects Salmonella against nitrooxidative stress

Travis J. Bourret, Lin Liu, Jeff A. Shaw, Maroof Husain, Andrés Vázquez-Torres

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The PhoPQ two-component regulatory system coordinates the response of Salmonella enterica serovar Typhimurium to diverse environmental challenges encountered during infection of hosts, including changes in Mg2+ concentrations, pH, and antimicrobial peptides. Moreover, PhoPQ-dependent regulation of gene expression promotes intracellular survival of Salmonella in macrophages, and contributes to the resistance of this pathogen to reactive nitrogen species (RNS) generated from the nitric oxide produced by the inducible nitric oxide (NO) synthase of macrophages. We report here that Salmonella strains with mutations of phoPQ are hypersensitive to killing by RNS generated in vitro. The increased susceptibility of phoQ Salmonella to RNS requires molecular O2 and coincides with the nitrotyrosine formation, the oxidation of [4Fe-4S] clusters of dehydratases, and DNA damage. Mutations of respiratory NADH dehydrogenases prevent nitrotyrosine formation and abrogate the cytotoxicity of RNS against phoQ Salmonella, presumably by limiting the formation of peroxynitrite (ONOO-) arising from the diffusion-limited reaction of exogenous NO and endogenous superoxide (O2 •-) produced in the electron transport chain. The mechanism underlying PhoPQ-mediated resistance to RNS is linked to the coordination of Mg2+ homeostasis through the PhoPQ-regulated MgtA transporter. Collectively, our investigations are consistent with a model in which PhoPQ-dependent Mg2+ homeostasis protects Salmonella against nitrooxidative stress.

Original languageEnglish (US)
Article number15083
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Reactive Nitrogen Species
Salmonella
Magnesium
Homeostasis
Nitric Oxide
Macrophages
Hydro-Lyases
NADH Dehydrogenase
Mutation
Peroxynitrous Acid
Salmonella enterica
Gene Expression Regulation
Nitric Oxide Synthase Type II
Electron Transport
Superoxides
DNA Damage
Peptides
Infection

All Science Journal Classification (ASJC) codes

  • General

Cite this

Magnesium homeostasis protects Salmonella against nitrooxidative stress. / Bourret, Travis J.; Liu, Lin; Shaw, Jeff A.; Husain, Maroof; Vázquez-Torres, Andrés.

In: Scientific Reports, Vol. 7, No. 1, 15083, 01.12.2017.

Research output: Contribution to journalArticle

Bourret, Travis J. ; Liu, Lin ; Shaw, Jeff A. ; Husain, Maroof ; Vázquez-Torres, Andrés. / Magnesium homeostasis protects Salmonella against nitrooxidative stress. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
@article{c29502eb992d4fdba3dace1e15f73745,
title = "Magnesium homeostasis protects Salmonella against nitrooxidative stress",
abstract = "The PhoPQ two-component regulatory system coordinates the response of Salmonella enterica serovar Typhimurium to diverse environmental challenges encountered during infection of hosts, including changes in Mg2+ concentrations, pH, and antimicrobial peptides. Moreover, PhoPQ-dependent regulation of gene expression promotes intracellular survival of Salmonella in macrophages, and contributes to the resistance of this pathogen to reactive nitrogen species (RNS) generated from the nitric oxide produced by the inducible nitric oxide (NO) synthase of macrophages. We report here that Salmonella strains with mutations of phoPQ are hypersensitive to killing by RNS generated in vitro. The increased susceptibility of phoQ Salmonella to RNS requires molecular O2 and coincides with the nitrotyrosine formation, the oxidation of [4Fe-4S] clusters of dehydratases, and DNA damage. Mutations of respiratory NADH dehydrogenases prevent nitrotyrosine formation and abrogate the cytotoxicity of RNS against phoQ Salmonella, presumably by limiting the formation of peroxynitrite (ONOO-) arising from the diffusion-limited reaction of exogenous NO and endogenous superoxide (O2 •-) produced in the electron transport chain. The mechanism underlying PhoPQ-mediated resistance to RNS is linked to the coordination of Mg2+ homeostasis through the PhoPQ-regulated MgtA transporter. Collectively, our investigations are consistent with a model in which PhoPQ-dependent Mg2+ homeostasis protects Salmonella against nitrooxidative stress.",
author = "Bourret, {Travis J.} and Lin Liu and Shaw, {Jeff A.} and Maroof Husain and Andr{\'e}s V{\'a}zquez-Torres",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-15445-y",
language = "English (US)",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Magnesium homeostasis protects Salmonella against nitrooxidative stress

AU - Bourret, Travis J.

AU - Liu, Lin

AU - Shaw, Jeff A.

AU - Husain, Maroof

AU - Vázquez-Torres, Andrés

PY - 2017/12/1

Y1 - 2017/12/1

N2 - The PhoPQ two-component regulatory system coordinates the response of Salmonella enterica serovar Typhimurium to diverse environmental challenges encountered during infection of hosts, including changes in Mg2+ concentrations, pH, and antimicrobial peptides. Moreover, PhoPQ-dependent regulation of gene expression promotes intracellular survival of Salmonella in macrophages, and contributes to the resistance of this pathogen to reactive nitrogen species (RNS) generated from the nitric oxide produced by the inducible nitric oxide (NO) synthase of macrophages. We report here that Salmonella strains with mutations of phoPQ are hypersensitive to killing by RNS generated in vitro. The increased susceptibility of phoQ Salmonella to RNS requires molecular O2 and coincides with the nitrotyrosine formation, the oxidation of [4Fe-4S] clusters of dehydratases, and DNA damage. Mutations of respiratory NADH dehydrogenases prevent nitrotyrosine formation and abrogate the cytotoxicity of RNS against phoQ Salmonella, presumably by limiting the formation of peroxynitrite (ONOO-) arising from the diffusion-limited reaction of exogenous NO and endogenous superoxide (O2 •-) produced in the electron transport chain. The mechanism underlying PhoPQ-mediated resistance to RNS is linked to the coordination of Mg2+ homeostasis through the PhoPQ-regulated MgtA transporter. Collectively, our investigations are consistent with a model in which PhoPQ-dependent Mg2+ homeostasis protects Salmonella against nitrooxidative stress.

AB - The PhoPQ two-component regulatory system coordinates the response of Salmonella enterica serovar Typhimurium to diverse environmental challenges encountered during infection of hosts, including changes in Mg2+ concentrations, pH, and antimicrobial peptides. Moreover, PhoPQ-dependent regulation of gene expression promotes intracellular survival of Salmonella in macrophages, and contributes to the resistance of this pathogen to reactive nitrogen species (RNS) generated from the nitric oxide produced by the inducible nitric oxide (NO) synthase of macrophages. We report here that Salmonella strains with mutations of phoPQ are hypersensitive to killing by RNS generated in vitro. The increased susceptibility of phoQ Salmonella to RNS requires molecular O2 and coincides with the nitrotyrosine formation, the oxidation of [4Fe-4S] clusters of dehydratases, and DNA damage. Mutations of respiratory NADH dehydrogenases prevent nitrotyrosine formation and abrogate the cytotoxicity of RNS against phoQ Salmonella, presumably by limiting the formation of peroxynitrite (ONOO-) arising from the diffusion-limited reaction of exogenous NO and endogenous superoxide (O2 •-) produced in the electron transport chain. The mechanism underlying PhoPQ-mediated resistance to RNS is linked to the coordination of Mg2+ homeostasis through the PhoPQ-regulated MgtA transporter. Collectively, our investigations are consistent with a model in which PhoPQ-dependent Mg2+ homeostasis protects Salmonella against nitrooxidative stress.

UR - http://www.scopus.com/inward/record.url?scp=85033388947&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033388947&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-15445-y

DO - 10.1038/s41598-017-15445-y

M3 - Article

C2 - 29118452

AN - SCOPUS:85033388947

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 15083

ER -