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Infection and Immunity, January 2006, p. 56-63, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.56-63.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Dihydrolipoamide Acyltransferase Is Critical for Mycobacterium tuberculosis Pathogenesis

Shuangping Shi and Sabine Ehrt*

Department of Microbiology and Immunology, Program in Immunology and Microbial Pathogenesis, Weill Medical College of Cornell University, New York, New York 10021

Received 2 June 2005/ Returned for modification 10 July 2005/ Accepted 18 September 2005

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 (H37Rv{Delta}dlaT) that displayed phenotypes associated with DlaT's role in metabolism and in defense against nitrosative stress. The H37Rv{Delta}dlaT strain showed retarded growth in vitro and was highly susceptible to killing by acidified sodium nitrite. Mouse macrophages readily killed intracellular H37Rv{Delta}dlaT organisms, and in mice dlaT was required for full virulence.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Weill Cornell Medical College, Box 62, 1300 York Avenue, New York, NY 10021. Phone: (212) 746-2994. Fax: (212) 746-8587. E-mail: sae2004{at}med.cornell.edu.

Editor: J. L. Flynn

Infection and Immunity, January 2006, p. 56-63, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.56-63.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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