Dihydrolipoamide acyltransferase is critical for Mycobacterium tuberculosis pathogenesis.

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Shi S, Ehrt S

Dihydrolipoamide acyltransferase is critical for Mycobacterium tuberculosis pathogenesis.

Infect Immun. 2006 Jan;74(1):56-63.

PubMed ID

16368957 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
NADH	Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial	Protein	Humans	Unknown	Not Available	Details