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Evidence for genes associated with the ability of Mycobacterium avium subsp. hominissuis to escape apoptotic macrophages

Mycobacterium avium subsp. hominissuis (MAH) is an environmental bacteria that infects immunocompromised humans. MAH cases are increasing in incidence, making it crucial to gain knowledge of the pathogenic mechanisms associated with the bacterium. MAH infects macrophages and after several days the i...

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Autores principales: Bermudez, Luiz E., Danelishvili, Lia, Babrack, Lmar, Pham, Tuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548235/
https://www.ncbi.nlm.nih.gov/pubmed/26380226
http://dx.doi.org/10.3389/fcimb.2015.00063
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author Bermudez, Luiz E.
Danelishvili, Lia
Babrack, Lmar
Pham, Tuan
author_facet Bermudez, Luiz E.
Danelishvili, Lia
Babrack, Lmar
Pham, Tuan
author_sort Bermudez, Luiz E.
collection PubMed
description Mycobacterium avium subsp. hominissuis (MAH) is an environmental bacteria that infects immunocompromised humans. MAH cases are increasing in incidence, making it crucial to gain knowledge of the pathogenic mechanisms associated with the bacterium. MAH infects macrophages and after several days the infection triggers the phagocyte apoptosis. Many of the intracellular MAH escape the cell undergoing apoptosis leading to infection of neighboring macrophages. We screened a transposon bank of MAH mutants in U937 mononuclear phagocytes for the inability to escape macrophages undergoing apoptosis. Mutations in genes; MAV_2235, MAV_2120, MAV_2410, and MAV_4563 resulted in the inability of the bacteria to exit macrophages upon apoptosis. Complementation of the mutations corrected the phenotype either completely or partially. Testing for the ability of the mutants to survive in macrophages compared to the wild-type bacterium revealed that the mutant clones were not attenuated up to 4 days of infection. Testing in vivo, however, demonstrated that all the MAH clones were attenuated compared with the wild-type MAC 104 in tissues of mice. Although the mechanism associated with the bacterial inability to leave apoptotic macrophages is unknown, the identification of macrophage cytoplasm targets for the MAH proteins suggest that they interfere either with protein degradation machinery or post-translation mechanisms. The identification of tatC as a MAH protein involved in the ability of MAH to leave macrophages, suggests that secreted effector(s) are involved in the process. The study reveals a pathway of escape from macrophages, not shared with Mycobacterium tuberculosis.
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spelling pubmed-45482352015-09-14 Evidence for genes associated with the ability of Mycobacterium avium subsp. hominissuis to escape apoptotic macrophages Bermudez, Luiz E. Danelishvili, Lia Babrack, Lmar Pham, Tuan Front Cell Infect Microbiol Microbiology Mycobacterium avium subsp. hominissuis (MAH) is an environmental bacteria that infects immunocompromised humans. MAH cases are increasing in incidence, making it crucial to gain knowledge of the pathogenic mechanisms associated with the bacterium. MAH infects macrophages and after several days the infection triggers the phagocyte apoptosis. Many of the intracellular MAH escape the cell undergoing apoptosis leading to infection of neighboring macrophages. We screened a transposon bank of MAH mutants in U937 mononuclear phagocytes for the inability to escape macrophages undergoing apoptosis. Mutations in genes; MAV_2235, MAV_2120, MAV_2410, and MAV_4563 resulted in the inability of the bacteria to exit macrophages upon apoptosis. Complementation of the mutations corrected the phenotype either completely or partially. Testing for the ability of the mutants to survive in macrophages compared to the wild-type bacterium revealed that the mutant clones were not attenuated up to 4 days of infection. Testing in vivo, however, demonstrated that all the MAH clones were attenuated compared with the wild-type MAC 104 in tissues of mice. Although the mechanism associated with the bacterial inability to leave apoptotic macrophages is unknown, the identification of macrophage cytoplasm targets for the MAH proteins suggest that they interfere either with protein degradation machinery or post-translation mechanisms. The identification of tatC as a MAH protein involved in the ability of MAH to leave macrophages, suggests that secreted effector(s) are involved in the process. The study reveals a pathway of escape from macrophages, not shared with Mycobacterium tuberculosis. Frontiers Media S.A. 2015-08-25 /pmc/articles/PMC4548235/ /pubmed/26380226 http://dx.doi.org/10.3389/fcimb.2015.00063 Text en Copyright © 2015 Bermudez, Danelishvili, Babrack and Pham. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Bermudez, Luiz E.
Danelishvili, Lia
Babrack, Lmar
Pham, Tuan
Evidence for genes associated with the ability of Mycobacterium avium subsp. hominissuis to escape apoptotic macrophages
title Evidence for genes associated with the ability of Mycobacterium avium subsp. hominissuis to escape apoptotic macrophages
title_full Evidence for genes associated with the ability of Mycobacterium avium subsp. hominissuis to escape apoptotic macrophages
title_fullStr Evidence for genes associated with the ability of Mycobacterium avium subsp. hominissuis to escape apoptotic macrophages
title_full_unstemmed Evidence for genes associated with the ability of Mycobacterium avium subsp. hominissuis to escape apoptotic macrophages
title_short Evidence for genes associated with the ability of Mycobacterium avium subsp. hominissuis to escape apoptotic macrophages
title_sort evidence for genes associated with the ability of mycobacterium avium subsp. hominissuis to escape apoptotic macrophages
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548235/
https://www.ncbi.nlm.nih.gov/pubmed/26380226
http://dx.doi.org/10.3389/fcimb.2015.00063
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