TitleThe environment of "Mycobacterium avium subsp. hominissuis" microaggregates induces synthesis of small proteins associated with efficient infection of respiratory epithelial cells.
Publication TypeJournal Article
Year of Publication2015
AuthorsBabrak, L, Danelishvili, L, Rose, SJ, Kornberg, T, Bermudez, LE
JournalInfect Immun
Date Published2015 Feb
KeywordsAnimals, Bacterial Adhesion, Bacterial Proteins, Cell Line, Tumor, Epithelial Cells, Female, Humans, Immune Sera, Immunocompromised Host, Mice, Mice, Inbred C57BL, Mycobacterium avium, Mycobacterium Infections, Mycobacterium smegmatis, Oligonucleotide Array Sequence Analysis, Respiratory Mucosa, Respiratory Tract Infections, Vimentin

"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.

Alternate JournalInfect Immun
PubMed ID25422262
PubMed Central IDPMC4294266
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
R01 AI043199 / AI / NIAID NIH HHS / United States
AI 043199 / AI / NIAID NIH HHS / United States