Glutathione disulfide and S‐nitrosoglutathione detoxification by Mycobacteriumtuberculosis thioredoxin system

Abstract

a b s t r a c tMycobacterium tuberculosis resides within alveolar macrophages. These phagocytes produce reactive nitrogen and oxygen intermediates to combat the invading pathogens. The macrophage glutathione (GSH) pool reduces nitric oxide (NO) to S-nitrosoglutathione (GSNO). Both glutathione disulfide (GSSG) and GSNO possess mycobactericidal activities in vitro. In this study we demonstrate that M. tuberculosis thioredoxin system, comprises of thioredoxin reductase B2 and thioredoxin C reduces the oxidized form of the intracellular mycothiol (MSSM) and is able to efficiently reduce GSSG and GSNO in vitro. Our study suggests that the thioredoxin system provide a general reduction mechanism to cope with oxidative stress associated with the microbe's metabolism as well as to detoxify xenobiotics produced by the host.

Ergothioneine Maintains Redox and Bioenergetic Homeostasis Essential for Drug Susceptibility and Virulence of Mycobacterium tuberculosis

“…An important dissimilarity between the expression profiles of egtA/D and mshA mutants is that thioredoxin B ( trxB1 , Rv1471) and a putative thioredoxin-like gene ( trx , Rv0526) are upregulated in the mshA mutant , but not in the egtA/D mutants. This observation is consistent with the requirement of MSH for thioredoxins as reducing partners (Attarian et al, 2009). The majority of the differentially regulated genes (22 of 25) in the egtA/D and mshA mutants are downregulated.…”

Reduced susceptibility of clinical strains of Mycobacterium tuberculosis to reactive nitrogen species promotes survival in activated macrophages

“…tuberculosis adapted to resist NO. Such defence mechanisms are poorly defined but include upregulation of ahpC encoding alkyl hydroperoxide reductase subunit C [21, 26], lpd encoding lipoamide dehydrogenase [27], the thioredoxin systems [28], and the dormancy survival regulator DosR [29]. In an effort to identify potential mutations in the genes involved in the bacterial defence against NO, we sequenced all the isolates, but no explanation for the increased NO-tolerance in BTB 02–141 could be found.…”

WhiB5, a Transcriptional Regulator That Contributes to Mycobacterium tuberculosis Virulence and Reactivation

“…9). GSNO is converted into glutathione (GSH) and NO from bacterial thioredoxin (5) and is important in M. tuberculosis killing by activated macrophages (42). While its mechanism of action against M. tuberculosis has not been elucidated fully, it might involve both the toxic action of NO and that of GSH.…”