title: The mycobacterial P55 efflux pump is required for optimal growth on cholesterol.
abstract: Cholesterol catabolism is thought to be a key factor contributing to the pathogenesis of Mycobacterium tuberculosis. Previous epistasis and mutant screening studies predicted that the P55 efflux pump (Rv1410c) positively interacts with the Mce4 transporter, a major cholesterol import system of M. tuberculosis and is needed for optimal growth in vitro, in macrophages, and in vivo. Using a combination of cell growth kinetic techniques, cholesterol consumption, and [4-(14)C]cholesterol uptake studies, we demonstrated that the Mycobacterium bovis BCG rv1410c gene indeed is needed for optimal in vitro growth on cholesterol and other carbon sources. Our data, together with previous predictions, support hypotheses that the P55 efflux pump functions in maintaining general metabolism or as a subunit of the Mce4 transport apparatus (catalyzing its assembly or providing cell wall integrity) to allow more efficient cholesterol uptake.
authors.affiliation: a Department of Microbiology and Immunology; Center for Tuberculosis Research; Life Sciences Center; University of British Columbia ; Vancouver , BC , Canada.
authors.forename: Santiago
authors.initials: S
authors.lastname: Ramón-García
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Stewart
authors.forename: Zhao Kun
authors.initials: ZK
authors.lastname: Hui
authors.forename: William W
authors.initials: WW
authors.lastname: Mohn
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Thompson
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D019450:Genes, MDR; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D009163:Mycobacterium bovis / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C425143:P55 protein, Mycobacterium; D002784:Cholesterol
keywords: P55; Rv1410c; cholesterol; efflux pump; mycobacterium