The Genetic Requirements for Fast and Slow Growth in Mycobacteria

Mycobacterium tuberculosis infects a third of the world's population. Primary tuberculosis involving active fast bacterial replication is often followed by asymptomatic latent tuberculosis, which is characterised by slow or non-replicating bacteria. Reactivation of the latent infection involvin...

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Autores principales: Beste, Dany J. V., Espasa, Mateus, Bonde, Bhushan, Kierzek, Andrzej M., Stewart, Graham R., McFadden, Johnjoe
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685279/
https://www.ncbi.nlm.nih.gov/pubmed/19479006
http://dx.doi.org/10.1371/journal.pone.0005349
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author Beste, Dany J. V.
Espasa, Mateus
Bonde, Bhushan
Kierzek, Andrzej M.
Stewart, Graham R.
McFadden, Johnjoe
author_facet Beste, Dany J. V.
Espasa, Mateus
Bonde, Bhushan
Kierzek, Andrzej M.
Stewart, Graham R.
McFadden, Johnjoe
author_sort Beste, Dany J. V.
collection PubMed
description Mycobacterium tuberculosis infects a third of the world's population. Primary tuberculosis involving active fast bacterial replication is often followed by asymptomatic latent tuberculosis, which is characterised by slow or non-replicating bacteria. Reactivation of the latent infection involving a switch back to active bacterial replication can lead to post-primary transmissible tuberculosis. Mycobacterial mechanisms involved in slow growth or switching growth rate provide rational targets for the development of new drugs against persistent mycobacterial infection. Using chemostat culture to control growth rate, we screened a transposon mutant library by Transposon site hybridization (TraSH) selection to define the genetic requirements for slow and fast growth of Mycobacterium bovis (BCG) and for the requirements of switching growth rate. We identified 84 genes that are exclusively required for slow growth (69 hours doubling time) and 256 genes required for switching from slow to fast growth. To validate these findings we performed experiments using individual M. tuberculosis and M. bovis BCG knock out mutants. We have demonstrated that growth rate control is a carefully orchestrated process which requires a distinct set of genes encoding several virulence determinants, gene regulators, and metabolic enzymes. The mce1 locus appears to be a component of the switch to slow growth rate, which is consistent with the proposed role in virulence of M. tuberculosis. These results suggest novel perspectives for unravelling the mechanisms involved in the switch between acute and persistent TB infections and provide a means to study aspects of this important phenomenon in vitro.
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spelling pubmed-26852792009-05-27 The Genetic Requirements for Fast and Slow Growth in Mycobacteria Beste, Dany J. V. Espasa, Mateus Bonde, Bhushan Kierzek, Andrzej M. Stewart, Graham R. McFadden, Johnjoe PLoS One Research Article Mycobacterium tuberculosis infects a third of the world's population. Primary tuberculosis involving active fast bacterial replication is often followed by asymptomatic latent tuberculosis, which is characterised by slow or non-replicating bacteria. Reactivation of the latent infection involving a switch back to active bacterial replication can lead to post-primary transmissible tuberculosis. Mycobacterial mechanisms involved in slow growth or switching growth rate provide rational targets for the development of new drugs against persistent mycobacterial infection. Using chemostat culture to control growth rate, we screened a transposon mutant library by Transposon site hybridization (TraSH) selection to define the genetic requirements for slow and fast growth of Mycobacterium bovis (BCG) and for the requirements of switching growth rate. We identified 84 genes that are exclusively required for slow growth (69 hours doubling time) and 256 genes required for switching from slow to fast growth. To validate these findings we performed experiments using individual M. tuberculosis and M. bovis BCG knock out mutants. We have demonstrated that growth rate control is a carefully orchestrated process which requires a distinct set of genes encoding several virulence determinants, gene regulators, and metabolic enzymes. The mce1 locus appears to be a component of the switch to slow growth rate, which is consistent with the proposed role in virulence of M. tuberculosis. These results suggest novel perspectives for unravelling the mechanisms involved in the switch between acute and persistent TB infections and provide a means to study aspects of this important phenomenon in vitro. Public Library of Science 2009-04-28 /pmc/articles/PMC2685279/ /pubmed/19479006 http://dx.doi.org/10.1371/journal.pone.0005349 Text en Beste et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Beste, Dany J. V.
Espasa, Mateus
Bonde, Bhushan
Kierzek, Andrzej M.
Stewart, Graham R.
McFadden, Johnjoe
The Genetic Requirements for Fast and Slow Growth in Mycobacteria
title The Genetic Requirements for Fast and Slow Growth in Mycobacteria
title_full The Genetic Requirements for Fast and Slow Growth in Mycobacteria
title_fullStr The Genetic Requirements for Fast and Slow Growth in Mycobacteria
title_full_unstemmed The Genetic Requirements for Fast and Slow Growth in Mycobacteria
title_short The Genetic Requirements for Fast and Slow Growth in Mycobacteria
title_sort genetic requirements for fast and slow growth in mycobacteria
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685279/
https://www.ncbi.nlm.nih.gov/pubmed/19479006
http://dx.doi.org/10.1371/journal.pone.0005349
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