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Low‐molecular‐weight thiol‐dependent antioxidant and antinitrosative defences in S almonella pathogenesis
Author(s) -
Song Miryoung,
Husain Maroof,
JonesCarson Jessica,
Liu Lin,
Henard Calvin A.,
VázquezTorres Andrés
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12119
Subject(s) - glutathione , biochemistry , biology , reactive nitrogen species , antioxidant , reactive oxygen species , glutamine , glutamine amidotransferase , enzyme , s nitrosoglutathione , nitric oxide , mutant , oxidative stress , gene , amino acid , endocrinology
Summary We found herein that the intracytoplasmic pool of the low‐molecular‐weight ( LMW ) thiol glutathione ( GSH ) is readily oxidized in S almonella 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 S almonella 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 S almonella . An acute model of salmonellosis has revealed that the antioxidant and antinitrosative properties associated with the GSH biosynthetic pathway represent a first line of S almonella resistance against reactive oxygen and nitrogen species engendered in the context of a functional NRAMP 1 R divalent metal transporter.