Low-molecular-weight thiol-dependent antioxidant and antinitrosative defences in Salmonella pathogenesis.

Abstract

We found herein that the intracytoplasmic pool of the low-molecular-weight (LMW) thiol glutathione (GSH) is readily oxidized in Salmonella exposed to nitric oxide (NO). The hypersusceptibility of gshA and gshB mutants lacking γ-glutamylcysteine and glutathione synthetases to NO and S-nitrosoglutathione indicates that GSH antagonizes the bacteriostatic activity of reactive nitrogen species. Metabolites of the GSH biosynthetic pathway do not affect the enzymatic activity of classical NO targets such as quinol oxidases. In contrast, LMW thiols diminish the nitrosative stress experienced by enzymes, such as glutamine oxoglutarate amidotransferase, that contain redox active cysteines. LMW thiols also preserve the transcription of Salmonella pathogenicity island 2 gene targets from the inhibitory activity of nitrogen oxides. These findings are consistent with the idea that GSH scavenges reactive nitrogen species (RNS) other than NO. Compared with the adaptive response afforded by inducible systems such as the hmp-encoded flavohaemoprotein, gshA, encoding the first step of GSH biosynthesis, is constitutively expressed in Salmonella. An acute model of salmonellosis has revealed that the antioxidant and antinitrosative properties associated with the GSH biosynthetic pathway represent a first line of Salmonella resistance against reactive oxygen and nitrogen species engendered in the context of a functional NRAMP1(R) divalent metal transporter.

• Authors: Miryoung Song, Maroof Husain, Jessica Jones-Carson, Lin Liu, Calvin A Henard, Andrés Vázquez-Torres
• Journal: Molecular microbiology (Mol Microbiol) Vol. 87 Issue 3 Pg. 609-22 (Feb 2013) ISSN: 1365-2958 [Electronic] England
• PMID: 23217033 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

• Oxidants
• Reactive Nitrogen Species
• Reactive Oxygen Species
• Sulfhydryl Compounds
• Nitric Oxide
• Glutathione

Topics

• Glutathione (metabolism)
• Molecular Weight
• Nitric Oxide (antagonists & inhibitors, metabolism)
• Nitrosation
• Oxidants (antagonists & inhibitors, metabolism)
• Oxidation-Reduction
• Reactive Nitrogen Species (antagonists & inhibitors)
• Reactive Oxygen Species (antagonists & inhibitors)
• Salmonella (drug effects, metabolism, physiology)
• Sulfhydryl Compounds (metabolism)