title: Host cell-induced components of the sulfate assimilation pathway are major protective antigens of Mycobacterium tuberculosis.
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.
authors.affiliation: Mycobacterial Research Program, Centenary Institute, Newtown, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Pinto
authors.forename: Lisa
authors.initials: L
authors.lastname: Leotta
authors.forename: Erin R
authors.initials: ER
authors.lastname: Shanahan
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: West
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Leyh
authors.forename: Warwick
authors.initials: W
authors.lastname: Britton
authors.forename: James A
authors.initials: JA
authors.lastname: Triccas
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013431:Sulfates / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology; D015854:Up-Regulation; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D013431:Sulfates; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit