Characterization of a Clp protease gene regulator and the reaeration response in Mycobacterium tuberculosis.
Mycobacterium tuberculosis (MTB) enters a non-replicating state when exposed to low oxygen tension, a condition the bacillus encounters in granulomas during infection. Determining how mycobacteria enter and maintain this state is a major focus of research. However, from a public health standpoint th...
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doaj-2a44add161324c80bd578ac7de9bfaa42020-11-24T21:55:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0157e1162210.1371/journal.pone.0011622Characterization of a Clp protease gene regulator and the reaeration response in Mycobacterium tuberculosis.Ashley M SherridTige R RustadGerard A CangelosiDavid R ShermanMycobacterium tuberculosis (MTB) enters a non-replicating state when exposed to low oxygen tension, a condition the bacillus encounters in granulomas during infection. Determining how mycobacteria enter and maintain this state is a major focus of research. However, from a public health standpoint the importance of latent TB is its ability to reactivate. The mechanism by which mycobacteria return to a replicating state upon re-exposure to favorable conditions is not understood. In this study, we utilized reaeration from a defined hypoxia model to characterize the adaptive response of MTB following a return to favorable growth conditions. Global transcriptional analysis identified the approximately 100 gene Reaeration Response, induced relative to both log-phase and hypoxic MTB. This response includes chaperones and proteases, as well as the transcription factor Rv2745c, which we characterize as a Clp protease gene regulator (ClgR) orthologue. During reaeration, genes repressed during hypoxia are also upregulated in a wave of transcription that includes genes crucial to transcription, translation and oxidative phosphorylation and culminates in bacterial replication. In sum, this study defines a new transcriptional response of MTB with potential relevance to disease, and implicates ClgR as a regulator involved in resumption of replication following hypoxia.http://europepmc.org/articles/PMC2905415?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ashley M Sherrid Tige R Rustad Gerard A Cangelosi David R Sherman |
spellingShingle |
Ashley M Sherrid Tige R Rustad Gerard A Cangelosi David R Sherman Characterization of a Clp protease gene regulator and the reaeration response in Mycobacterium tuberculosis. PLoS ONE |
author_facet |
Ashley M Sherrid Tige R Rustad Gerard A Cangelosi David R Sherman |
author_sort |
Ashley M Sherrid |
title |
Characterization of a Clp protease gene regulator and the reaeration response in Mycobacterium tuberculosis. |
title_short |
Characterization of a Clp protease gene regulator and the reaeration response in Mycobacterium tuberculosis. |
title_full |
Characterization of a Clp protease gene regulator and the reaeration response in Mycobacterium tuberculosis. |
title_fullStr |
Characterization of a Clp protease gene regulator and the reaeration response in Mycobacterium tuberculosis. |
title_full_unstemmed |
Characterization of a Clp protease gene regulator and the reaeration response in Mycobacterium tuberculosis. |
title_sort |
characterization of a clp protease gene regulator and the reaeration response in mycobacterium tuberculosis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2010-01-01 |
description |
Mycobacterium tuberculosis (MTB) enters a non-replicating state when exposed to low oxygen tension, a condition the bacillus encounters in granulomas during infection. Determining how mycobacteria enter and maintain this state is a major focus of research. However, from a public health standpoint the importance of latent TB is its ability to reactivate. The mechanism by which mycobacteria return to a replicating state upon re-exposure to favorable conditions is not understood. In this study, we utilized reaeration from a defined hypoxia model to characterize the adaptive response of MTB following a return to favorable growth conditions. Global transcriptional analysis identified the approximately 100 gene Reaeration Response, induced relative to both log-phase and hypoxic MTB. This response includes chaperones and proteases, as well as the transcription factor Rv2745c, which we characterize as a Clp protease gene regulator (ClgR) orthologue. During reaeration, genes repressed during hypoxia are also upregulated in a wave of transcription that includes genes crucial to transcription, translation and oxidative phosphorylation and culminates in bacterial replication. In sum, this study defines a new transcriptional response of MTB with potential relevance to disease, and implicates ClgR as a regulator involved in resumption of replication following hypoxia. |
url |
http://europepmc.org/articles/PMC2905415?pdf=render |
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