SecA2 functions in the secretion of superoxide dismutase A and in the virulence of Mycobacterium tuberculosis

Miriam Braunstein, Benjamin J. Espinosa, John Chan, John T. Belisle, William R. Jacobs

Research output: Contribution to journalArticle

177 Citations (Scopus)

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 ΔsecA2 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.

Original languageEnglish (US)
Pages (from-to)453-464
Number of pages12
JournalMolecular Microbiology
Volume48
Issue number2
DOIs
StatePublished - Apr 2003

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Mycobacterium tuberculosis
Superoxide Dismutase
Virulence
Tuberculosis
Proteins
Housekeeping
Secretory Pathway
Gene Deletion
Virulence Factors
Mycobacterium
Protein Sorting Signals
Macrophages
Bacteria
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

SecA2 functions in the secretion of superoxide dismutase A and in the virulence of Mycobacterium tuberculosis. / Braunstein, Miriam; Espinosa, Benjamin J.; Chan, John; Belisle, John T.; Jacobs, William R.

In: Molecular Microbiology, Vol. 48, No. 2, 04.2003, p. 453-464.

Research output: Contribution to journalArticle

Braunstein, Miriam ; Espinosa, Benjamin J. ; Chan, John ; Belisle, John T. ; Jacobs, William R. / SecA2 functions in the secretion of superoxide dismutase A and in the virulence of Mycobacterium tuberculosis. In: Molecular Microbiology. 2003 ; Vol. 48, No. 2. pp. 453-464.
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