title: Inactivation of the Mycobacterium tuberculosis Nramp orthologue (mntH) does not affect virulence in a mouse model of tuberculosis.
abstract: Mycobacterium tuberculosis is an intracellular pathogen which can survive and multiply within the phagosomal compartment of the macrophage, and in doing so has to withstand the various macrophage defense mechanisms, which include limitation of iron and other metals. Analysis of the complete genome sequence of M. tuberculosis revealed an extensive array of cation transporters, including mntH, an orthologue of the eukaryotic Nramp (natural resistance-associated macrophage protein) gene, that encodes a proton-dependent divalent metal transporter. To assess the effect of this transporter on intracellular survival and pathogenesis, an mntH knock-out mutant of M. tuberculosis H37Rv was created and assayed in bone marrow-derived macrophages and in a murine model of tuberculosis. In neither of these systems was any loss of fitness associated with inactivation of mntH, demonstrating that Nramp orthologues are not important determinants of mycobacterial virulence.
authors.affiliation: Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: P
authors.initials: P
authors.lastname: Domenech
authors.forename: A S
authors.initials: AS
authors.lastname: Pym
authors.forename: M
authors.initials: M
authors.lastname: Cellier
authors.forename: C E
authors.initials: CE
authors.lastname: Barry
authors.forename: S T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D001853:Bone Marrow; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D017353:Gene Deletion; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D014376:Tuberculosis / Q000382:microbiology* / Q000503:physiopathology; D014774:Virulence; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; C433793:MntH protein, bacteria