The Environment of “Mycobacterium avium subsp. hominissuis” Microaggregates Induces Synthesis of Small Proteins Associated with Efficient Infection of Respiratory Epithelial Cells

Author:

Babrak Lmar,Danelishvili Lia,Rose Sasha J.,Kornberg Tiffany,Bermudez Luiz E.

Abstract

Mycobacterium aviumsubsp.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 treatM. aviumsubsp.hominissuisinfection in the lungs. During initial colonization of the airways,M. aviumsubsp.hominissuisforms microaggregates composed of 3 to 20 bacteria on human respiratory epithelial cells, which provides an environment for phenotypic changes leading to efficient mucosal invasionin vitroandin 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 noninvasiveMycobacterium 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 forM. aviumsubsp.hominissuisadherence to the host cell. MBP-1 immune serum significantly inhibitedM. aviumsubsp.hominissuisinfection throughout the respiratory tracts of mice. This study characterizes a pathogenic mechanism utilized byM. aviumsubsp.hominissuisto bind and invade the host respiratory epithelium, suggesting new potential targets for the development of antivirulence therapy.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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