title: Identification of Mycobacterium avium genes expressed during in vivo infection and the role of the oligopeptide transporter OppA in virulence.
abstract: Mycobacterium avium causes disseminated disease in patients with AIDS and other immunosuppressive conditions and pulmonary infections in individuals with chronic lung diseases. Much still need to be learn about the mechanisms of M. avium pathogenesis. Using a mouse model of disseminated M. avium disease, we applied an in vivo expression technology system and identified M. avium genes up-regulated in different organs of mice during early stage of infection. The M. avium oppA gene, involved in an active transport of oligopeptides across the cell membrane, was found highly expressed in lung, liver and spleen of mice. Mutation in the transport domain of the oppA gene resulted in bacterial attenuation in both macrophages and in mice. Using protein-protein interaction assay, it was determined that two hypothetical small proteins, MAV_2941 (73aa) and MAV_4320 (45aa), interact with OppA. MAV_2941 was shown to be secreted by the bacterium into the macrophage cytoplasm. Mutations in MAV_2941 was associated with significant impairment of growth in macrophages. Understanding the mechanisms involved in the functions of MAV_2941 and MAV_4320 is warranted.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Lia
authors.initials: L
authors.lastname: Danelishvili
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Stang
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA; Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA; Department of Microbiology, College of Science, Oregon State University, Corvallis, OR 97331, USA; Molecular and Cell Biology Program, College of Science, Oregon State University, Corvallis, OR 97331, USA. Electronic address: luiz.bermudez@oregonstate.edu.
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Bermudez
mesh_terms: D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005798:Genes, Bacterial; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009162:Mycobacterium avium / Q000235:genetics* / Q000254:growth & development* / Q000302:isolation & purification; D009842:Oligopeptides / Q000378:metabolism; D014376:Tuberculosis / Q000382:microbiology*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D008074:Lipoproteins; D050505:Mutant Proteins; D009842:Oligopeptides; D037521:Virulence Factors; C046506:oligopeptide-binding protein, bacteria
keywords: IVET system; In vivo; Mycobacterium avium; Virulence genes