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PMID: 12694625 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis.

Molecular microbiology ·Vol. 48 ·No. 3 ·2003-05-00 ·Pages 833-43

Park HD, Guinn KM, Harrell MI, Liao R, Voskuil MI, Tompa M, Schoolnik GK, Sherman DR

Abstract

Unlike many pathogens that are overtly harmful to their hosts, Mycobacterium tuberculosis can persist for years within humans in a clinically latent state. Latency is often linked to hypoxic conditions within the host. Among M. tuberculosis genes induced by hypoxia is a putative transcription factor, Rv3133c/DosR. We performed targeted disruption of this locus followed by transcriptome analysis of wild-type and mutant bacilli. Nearly all the genes powerfully regulated by hypoxia require Rv3133c/DosR for their induction. Computer analysis identified a consensus motif, a variant of which is located upstream of nearly all M. tuberculosis genes rapidly induced by hypoxia. Further, Rv3133c/DosR binds to the two copies of this motif upstream of the hypoxic response gene alpha-crystallin. Mutations within the binding sites abolish both Rv3133c/DosR binding as well as hypoxic induction of a downstream reporter gene. Also, mutation experiments with Rv3133c/DosR confirmed sequence-based predictions that the C-terminus is responsible for DNA binding and that the aspartate at position 54 is essential for function. Together, these results demonstrate that Rv3133c/DosR is a transcription factor of the two-component response regulator class, and that it is the primary mediator of a hypoxic signal within M. tuberculosis.

MeSH Terms
Aspartic Acid/metabolism Bacterial Proteins/genetics,metabolism Gene Expression Regulation, Bacterial Gene Targeting Genes, Reporter Humans Hypoxia/metabolism Mycobacterium tuberculosis/genetics,metabolism Oligonucleotide Array Sequence Analysis Oxygen/metabolism Protein Binding Regulatory Sequences, Nucleic Acid Transcription Factors/genetics,metabolism Tuberculosis/metabolism
Chemicals
Bacterial Proteins Transcription Factors Aspartic Acid Oxygen
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Park Heui-Dong
Department of Pathobiology, University of Washington, Seattle, WA 98195, USA.
Guinn Kristi M
Harrell Maria I
Liao Reiling
Voskuil Martin I
Tompa Martin
Schoolnik Gary K
Sherman David R
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Article Info
Journal
Molecular microbiology
Abbr.
Mol Microbiol
ISSN
0950-382X
DOI
10.1046/j.1365-2958.2003.03474.x
Published
2003-05-00
Pages
833-43
Language
English
Region
England
NLM ID
8712028
PMCID
PMC1992516
Subset
IM
Grants
NIAID NIH HHS · R01 AI047744 · United States
NIAID NIH HHS · AI47744 · United States
NIAID NIH HHS · R01 AI044826 · United States
NHGRI NIH HHS · HG02602-01 · United States
NHGRI NIH HHS · R01 HG002602 · United States
NIAID NIH HHS · AI44826 · United States
NIAID NIH HHS · R21 AI047744 · United States
External Links
PubMed source DOI: 10.1046/j.1365-2958.2003.03474.x PMC Full Text View journal details
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