title: BacA, an ABC transporter involved in maintenance of chronic murine infections with Mycobacterium tuberculosis.
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 Mycobacterium tuberculosis (Rv1819c), we insertionally inactivated this gene and analyzed the resulting mutant for a variety of phenotypes. BacA deficiency in M. tuberculosis 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 a profound effect on maintenance of extended chronic infection and ultimate outcome. As in alphaproteobacteria, deletion of BacA in M. tuberculosis led to increased bleomycin resistance, and heterologous expression of the M. tuberculosis BacA homolog in Escherichia 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.
authors.affiliation: Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, 33 North Drive, Bethesda, Maryland 20892, USA.
authors.forename: Pilar
authors.initials: P
authors.lastname: Domenech
authors.forename: Hajime
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Kristin
authors.initials: K
authors.lastname: LeVier
authors.forename: Graham C
authors.initials: GC
authors.lastname: Walker
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001761:Bleomycin / Q000494:pharmacology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D010802:Phylogeny; D014376:Tuberculosis / Q000382:microbiology*; D014774:Virulence
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D001761:Bleomycin