Low‐molecular‐weight thiol‐dependent antioxidant and antinitrosative defences in Salmonella pathogenesis. Issue 3 (21st December 2012)

• Record Type: Journal Article
• Authors: Song, Miryoung; Husain, Maroof; Jones‐Carson, Jessica; Liu, Lin; Henard, Calvin A.; Vázquez‐Torres, Andrés
• Is Part Of: Molecular microbiology. Volume 87:Issue 3(2013)
• Page Start: 609
• Page End: 622
• Publication Date: 2012-12-21
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12119
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>We found herein that the intracytoplasmic pool of the low‐molecular‐weight (LMW) thiol glutathione (GSH) is readily oxidized in <italic>Salmonella</italic> exposed to nitric oxide (NO). The hypersusceptibility of <italic>gshA</italic> and <italic>gshB</italic> mutants lacking γ‐glutamylcysteine and glutathione synthetases to NO and <italic>S</italic>‐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 <italic>Salmonella</italic> 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 <italic>hmp</italic>‐encoded flavohaemoprotein, <italic>gshA</italic>, encoding the first step of GSH biosynthesis, is constitutively expressed in <italic>Salmonella</italic>. An acute model of salmonellosis has revealed that the antioxidant and antinitrosative properties associated with the GSH biosynthetic pathway represent a first line of <italic>Salmonella</italic> resistance against reactive oxygen and nitrogen species engendered in the context of a functional NRAMP1<sup>R</sup> divalent metal transporter.</p> </abstract>