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Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis

Mycobacterium kansasii is an environmental nontuberculous mycobacterium that causes opportunistic tuberculosis-like disease. It is one of the most closely related species to the Mycobacterium tuberculosis complex. Using M. kansasii as a proxy for the M. kansasii-M. tuberculosis common ancestor, we a...

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Autores principales: Ghanem, Marwan, Dubé, Jean-Yves, Wang, Joyce, McIntosh, Fiona, Houle, Daniel, Domenech, Pilar, Reed, Michael B., Raman, Sahadevan, Buter, Jeffrey, Minnaard, Adriaan J., Moody, D. Branch, Behr, Marcel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587436/
https://www.ncbi.nlm.nih.gov/pubmed/33082253
http://dx.doi.org/10.1128/mBio.02645-20
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author Ghanem, Marwan
Dubé, Jean-Yves
Wang, Joyce
McIntosh, Fiona
Houle, Daniel
Domenech, Pilar
Reed, Michael B.
Raman, Sahadevan
Buter, Jeffrey
Minnaard, Adriaan J.
Moody, D. Branch
Behr, Marcel A.
author_facet Ghanem, Marwan
Dubé, Jean-Yves
Wang, Joyce
McIntosh, Fiona
Houle, Daniel
Domenech, Pilar
Reed, Michael B.
Raman, Sahadevan
Buter, Jeffrey
Minnaard, Adriaan J.
Moody, D. Branch
Behr, Marcel A.
author_sort Ghanem, Marwan
collection PubMed
description Mycobacterium kansasii is an environmental nontuberculous mycobacterium that causes opportunistic tuberculosis-like disease. It is one of the most closely related species to the Mycobacterium tuberculosis complex. Using M. kansasii as a proxy for the M. kansasii-M. tuberculosis common ancestor, we asked whether introducing the M. tuberculosis-specific gene pair Rv3377c-Rv3378c into M. kansasii affects the course of experimental infection. Expression of these genes resulted in the production of an adenosine-linked lipid species, known as 1-tuberculosinyladenosine (1-TbAd), but did not alter growth in vitro under standard conditions. Production of 1-TbAd enhanced growth of M. kansasii under acidic conditions through a bacterial cell-intrinsic mechanism independent of controlling pH in the bulk extracellular and intracellular spaces. Production of 1-TbAd led to greater burden of M. kansasii in the lungs of C57BL/6 mice during the first 24 h after infection, and ex vivo infections of alveolar macrophages recapitulated this phenotype within the same time frame. However, in long-term infections, production of 1-TbAd resulted in impaired bacterial survival in both C57BL/6 mice and Ccr2(−/−) mice. We have demonstrated that M. kansasii is a valid surrogate of M. tuberculosis to study virulence factors acquired by the latter organism, yet shown the challenge inherent to studying the complex evolution of mycobacterial pathogenicity with isolated gene complementation.
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spelling pubmed-75874362020-12-01 Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis Ghanem, Marwan Dubé, Jean-Yves Wang, Joyce McIntosh, Fiona Houle, Daniel Domenech, Pilar Reed, Michael B. Raman, Sahadevan Buter, Jeffrey Minnaard, Adriaan J. Moody, D. Branch Behr, Marcel A. mBio Research Article Mycobacterium kansasii is an environmental nontuberculous mycobacterium that causes opportunistic tuberculosis-like disease. It is one of the most closely related species to the Mycobacterium tuberculosis complex. Using M. kansasii as a proxy for the M. kansasii-M. tuberculosis common ancestor, we asked whether introducing the M. tuberculosis-specific gene pair Rv3377c-Rv3378c into M. kansasii affects the course of experimental infection. Expression of these genes resulted in the production of an adenosine-linked lipid species, known as 1-tuberculosinyladenosine (1-TbAd), but did not alter growth in vitro under standard conditions. Production of 1-TbAd enhanced growth of M. kansasii under acidic conditions through a bacterial cell-intrinsic mechanism independent of controlling pH in the bulk extracellular and intracellular spaces. Production of 1-TbAd led to greater burden of M. kansasii in the lungs of C57BL/6 mice during the first 24 h after infection, and ex vivo infections of alveolar macrophages recapitulated this phenotype within the same time frame. However, in long-term infections, production of 1-TbAd resulted in impaired bacterial survival in both C57BL/6 mice and Ccr2(−/−) mice. We have demonstrated that M. kansasii is a valid surrogate of M. tuberculosis to study virulence factors acquired by the latter organism, yet shown the challenge inherent to studying the complex evolution of mycobacterial pathogenicity with isolated gene complementation. American Society for Microbiology 2020-10-20 /pmc/articles/PMC7587436/ /pubmed/33082253 http://dx.doi.org/10.1128/mBio.02645-20 Text en Copyright © 2020 Ghanem et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Ghanem, Marwan
Dubé, Jean-Yves
Wang, Joyce
McIntosh, Fiona
Houle, Daniel
Domenech, Pilar
Reed, Michael B.
Raman, Sahadevan
Buter, Jeffrey
Minnaard, Adriaan J.
Moody, D. Branch
Behr, Marcel A.
Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis
title Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis
title_full Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis
title_fullStr Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis
title_full_unstemmed Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis
title_short Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis
title_sort heterologous production of 1-tuberculosinyladenosine in mycobacterium kansasii models pathoevolution towards the transcellular lifestyle of mycobacterium tuberculosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587436/
https://www.ncbi.nlm.nih.gov/pubmed/33082253
http://dx.doi.org/10.1128/mBio.02645-20
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