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J Clin Invest 2007 Aug 1;117(8):2279-88

Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis.

Hinchey J, Lee S, Jeon BY, Basaraba RJ, Venkataswamy MM, Chen B, Chan J, Braunstein M, Orme IM, Derrick SC, Morris SL, Jacobs WR, Porcelli SA

Jacobs WR (reprint author), Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, 1300 Morris Pk Ave, Bronx, NY 10461 USA Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10461 USA Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA Albert Einstein Coll Med, Dept Med, New York, NY USA Univ N Carolina, Dept Microbiol, Chapel Hill, NC USA


The inhibition of apoptosis of infected host cells is a well-known but poorly understood function of pathogenic mycobacteria. We show that inactivation of the secA2 gene in Mycobacterium tuberculosis, which encodes a component of a virulence-associated protein secretion system, enhanced the apoptosis of infected macrophages by diminishing secretion of mycobacterial superoxide dismutase. Deletion of secA2 markedly increased priming of antigen-specific CD8(+) T cells in vivo, and vaccination of mice and guinea pigs with a secA2 mutant significantly increased resistance to M. tuberculosis challenge compared with standard M. bovis bacille Calmette-Guérin vaccination. Our results define a mechanism for a key immune evasion strategy of M. tuberculosis and provide what we believe to be a novel approach for improving mycobacterial vaccines.

Category: Journal Article
PubMed ID: #17671656
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29