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J. Bacteriol. doi:10.1128/JB.01132-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

BacA: an ABC transporter involved in maintenance of chronic murine infections with Mycobacterium tuberculosis

Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Disease, 33 North Drive, Bethesda, MD 20892, USA.; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA

^* To whom correspondence should be addressed. Email: cbarry{at}niaid.nih.gov.

	Abstract

BacA is an inner-membrane protein associated with maintenance of chronic infections in several diverse host-pathogen interactions. To understand the function of the bacA gene in M. tuberculosis (Rv1819c) we insertionally inactivated this gene and analyzed the resulting mutant for a variety of phenotypes. BacA deficiency in M. tuberculosis (Mtb) did not affect sensitivity to detergents, acidic pH and zinc indicating that there was no global compromise in membrane integrity and a comprehensive evaluation of the major lipid constituents of the cell envelope failed to reveal any significant differences. Infection of mice with this mutant revealed no impact on establishment of infection but had a profound effect on maintenance of extended chronic infection and ultimate outcome. As in -proteobacteria, deletion of BacA in Mtb led to increased bleomycin resistance and heterologous expression of the Mtb BacA homolog in E. coli conferred sensitivity to antimicrobial peptides. These results suggest a striking conservation of function for BacA-related proteins in transport of a critical molecule that determines the outcome of the host-pathogen interaction.