Host cell-induced components of the sulfate assimilation pathway are major protective antigens of Mycobacterium tuberculosis

Rachel Pinto, Lisa Leotta, Erin R. Shanahan, Nicholas P. West, Thomas S. Leyh, Warwick Britton, James A. Triccas

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

New therapies to control tuberculosis are urgently required because of the inability of the only available vaccine, BCG, to adequately protect against tuberculosis. Here we demonstrate that proteins of the Mycobacterium tuberculosis sulfate-assimilation pathway (SAP) represent major immunogenic targets of the bacillus, as defined by strong T-cell recognition by both mice and humans infected with M. tuberculosis. SAP proteins displayed increased expression when M. tuberculosis was resident within host cells, which may account in part for their ability to stimulate anti-M. tuberculosis host immunity. Vaccination with the first enzyme in this pathway, adenosine-5′-triphosphate sulfurylase, conferred significant protection against murine tuberculosis and boosted BCG-induced protective immunity in the lung. Therefore, we have identified SAP components as a new family of M. tuberculosis antigens, and we have demonstrated that these components are promising candidate for inclusion in new vaccines to control tuberculosis in humans.

Original languageEnglish (US)
Pages (from-to)778-785
Number of pages8
JournalJournal of Infectious Diseases
Volume207
Issue number5
DOIs
StatePublished - Mar 1 2013

Keywords

  • ATP sulfurylase
  • human immune response
  • sulfate metabolism
  • tuberculosis
  • vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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