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Dihydrolipoamide acyltransferase is critical for Mycobacterium tuberculosis pathogenesis.

TitleDihydrolipoamide acyltransferase is critical for Mycobacterium tuberculosis pathogenesis.
Publication TypeJournal Article
Year of Publication2006
AuthorsShi S, Ehrt S
JournalInfect Immun
Volume74
Issue1
Pagination56-63
Date Published2006 Jan
ISSN0019-9567
KeywordsAcyltransferases, Animals, Cells, Cultured, Macrophage Activation, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, Mycobacterium tuberculosis, Nitric Oxide Synthase Type II, Tuberculosis
Abstract

Mycobacterium tuberculosis has evolved to persist in host macrophages, where it faces a nutrient-poor environment and is exposed to oxidative and nitrosative stress. To defend itself against oxidative/nitrosative stress, M. tuberculosis expresses an NADH-dependent peroxidase and peroxynitrite reductase that is encoded by ahpC, ahpD, lpd, and dlaT. In addition to its central role in the peroxynitrite reductase complex, dlaT (Rv2215) also encodes the E2 component of pyruvate dehydrogenase. Here we demonstrate that inactivation of dlaT in the chromosome of H37Rv resulted in a mutant (H37RvDeltadlaT) that displayed phenotypes associated with DlaT's role in metabolism and in defense against nitrosative stress. The H37RvDeltadlaT strain showed retarded growth in vitro and was highly susceptible to killing by acidified sodium nitrite. Mouse macrophages readily killed intracellular H37RvDeltadlaT organisms, and in mice dlaT was required for full virulence.

DOI10.1128/IAI.74.1.56-63.2006
Alternate JournalInfect Immun
PubMed ID16368957
PubMed Central IDPMC1346611
Grant ListR01 HL068525 / HL / NHLBI NIH HHS / United States

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