title: SecA2 functions in the secretion of superoxide dismutase A and in the virulence of Mycobacterium tuberculosis.
abstract: Tuberculosis remains a severe worldwide health threat. A thorough understanding of Mycobacterium tuberculosis pathogenesis will facilitate the development of new treatments for tuberculosis. Numerous bacterial pathogens possess specialized protein secretion systems that are dedicated to the export of virulence factors. Mycobacterium tuberculosis is part of a developing group of pathogenic bacteria that share the uncommon property of possessing two secA genes (secA1 and secA2). In mycobacteria, SecA1 is the essential 'housekeeping' SecA protein whereas SecA2 is an accessory secretion factor. Here we demonstrate that SecA2 contributes to the pathogenesis of M. tuberculosis. A deletion of the secA2 gene in M. tuberculosis attenuates the virulence of the organism in mice. By comparing the profile of proteins secreted by wild-type M. tuberculosis and the DeltasecA2 mutant, we identified superoxide dismutase A (SodA) as a protein dependent on SecA2 for secretion. SodA lacks a classical signal sequence for protein export. Our data suggests that SecA2-dependent export is a new type of secretion pathway that is part of a virulence mechanism of M. tuberculosis to elude the oxidative attack of macrophages.
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Braunstein
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Espinosa
authors.forename: John
authors.initials: J
authors.lastname: Chan
authors.forename: John T
authors.initials: JT
authors.lastname: Belisle
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D010544:Peroxidases / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D015996:Survival Rate; D014376:Tuberculosis / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016166:Free Radical Scavengers; D026901:Membrane Transport Proteins; D010544:Peroxidases; C076136:catalase HPI; C095500:SodA protein, Bacteria; D013482:Superoxide Dismutase; D000251:Adenosine Triphosphatases; C442123:SecA2 protein, Mycobacterium