title: An orphaned Mce-associated membrane protein of Mycobacterium tuberculosis is a virulence factor that stabilizes Mce transporters.
abstract: Mycobacterium tuberculosis proteins that are exported out of the bacterial cytoplasm are ideally positioned to be virulence factors; however, the functions of individual exported proteins remain largely unknown. Previous studies identified Rv0199 as an exported membrane protein of unknown function. Here, we characterized the role of Rv0199 in M. tuberculosis virulence using an aerosol model of murine infection. Rv0199 appears to be a member of a Mce-associated membrane (Mam) protein family leading us to rename it OmamA, for orphaned Mam protein A. Consistent with a role in Mce transport, we showed OmamA is required for cholesterol import, which is a Mce4-dependent process. We further demonstrated a function for OmamA in stabilizing protein components of the Mce1 transporter complex. These results indicate a function of OmamA in multiple Mce transporters and one that may be analogous to the role of VirB8 in stabilizing Type IV secretion systems, as structural similarities between Mam proteins and VirB8 proteins are predicted by the Phyre 2 program. In this study, we provide functional information about OmamA and shed light on the function of Mam family proteins in Mce transporters.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina.
authors.forename: Ellen Foot
authors.initials: EF
authors.lastname: Perkowski
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina.
authors.forename: Brittany K
authors.initials: BK
authors.lastname: Miller
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: McCann
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina.
authors.forename: Jonathan Tabb
authors.initials: JT
authors.lastname: Sullivan
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina.
authors.forename: Seidu
authors.initials: S
authors.lastname: Malik
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine.
authors.forename: Irving Coy
authors.initials: IC
authors.lastname: Allen
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Godfrey
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Hayden
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina.
authors.forename: Miriam
authors.initials: M
authors.lastname: Braunstein
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D017353:Gene Deletion; D023061:Gene Order; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D021381:Protein Transport; D014376:Tuberculosis / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D037521:Virulence Factors
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D037521:Virulence Factors; D002784:Cholesterol