title: The environment of "Mycobacterium avium subsp. hominissuis" microaggregates induces synthesis of small proteins associated with efficient infection of respiratory epithelial cells.
abstract: "Mycobacterium avium subsp. hominissuis" is an opportunistic environmental pathogen that causes respiratory illness in immunocompromised patients, such as those with cystic fibrosis as well as other chronic respiratory diseases. Currently, there is no efficient approach to prevent or treat M. avium subsp. hominissuis infection in the lungs. During initial colonization of the airways, M. avium subsp. hominissuis forms microaggregates composed of 3 to 20 bacteria on human respiratory epithelial cells, which provides an environment for phenotypic changes leading to efficient mucosal invasion in vitro and in vivo. DNA microarray analysis was employed to identify genes associated with the microaggregate phenotype. The gene encoding microaggregate-binding protein 1 (MBP-1) (MAV_3013) is highly expressed during microaggregate formation. When expressed in noninvasive Mycobacterium smegmatis, MBP-1 increased the ability of the bacteria to bind to HEp-2 epithelial cells. Using anti-MBP-1 immune serum, microaggregate binding to HEp-2 cells was significantly reduced. By far-Western blotting, and verified by coimmunoprecipitation, we observed that MBP-1 interacts with the host cytoskeletal protein vimentin. As visualized by confocal microscopy, microaggregates, as well as MBP-1, induced vimentin polymerization at the site of bacterium-host cell contact. Binding of microaggregates to HEp-2 cells was inhibited by treatment with an antivimentin antibody, suggesting that MBP-1 expression is important for M. avium subsp. hominissuis adherence to the host cell. MBP-1 immune serum significantly inhibited M. avium subsp. hominissuis infection throughout the respiratory tracts of mice. This study characterizes a pathogenic mechanism utilized by M. avium subsp. hominissuis to bind and invade the host respiratory epithelium, suggesting new potential targets for the development of antivirulence therapy.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA Department of Microbiology, College of Science, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Lmar
authors.initials: L
authors.lastname: Babrak
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Lia
authors.initials: L
authors.lastname: Danelishvili
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA Department of Microbiology, College of Science, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Sasha J
authors.initials: SJ
authors.lastname: Rose
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Kornberg
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA Department of Microbiology, College of Science, Oregon State University, Corvallis, Oregon, USA luiz.bermudez@oregonstate.edu.
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Bermudez
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics* / Q000276:immunology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology*; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D016867:Immunocompromised Host; D051379:Mice; D008810:Mice, Inbred C57BL; D009164:Mycobacterium Infections / Q000382:microbiology / Q000473:pathology; D009162:Mycobacterium avium / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020545:Respiratory Mucosa / Q000166:cytology / Q000382:microbiology*; D012141:Respiratory Tract Infections / Q000382:microbiology / Q000473:pathology; D014746:Vimentin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007106:Immune Sera; D014746:Vimentin