Cited by 719Tuberculosis Research and EpidemiologyBacterial Genetics and BiotechnologyMycobacterium research and diagnosis

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

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Park, Heui‐Dong, Guinn, Kristi M., Harrell, Maria I., Liao, Reiling, Voskuil, Martin I., Tompa, Martin, Schoolnik, Gary K., Sherman, David R.·2003·Molecular Microbiology

DOI 10.1046/j.1365-2958.2003.03474.xPMC PMC1992516

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Abstract

Summary: 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 .

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Authors: Park, H., Guinn, K. M., Harrell, M. I., Liao, R., Voskuil, M. I., Tompa, M., Schoolnik, G. K., & Sherman, D. R.
Affiliations: University of Washington (US)
Stanford Medicine (US)
Corresponding author: Sherman, David R.
ORCID: Voskuil, Martin I.
Sherman, David R.
Venue: Molecular Microbiology
Publisher: Wiley
Published: 2003-04-09
Volume: 48
Issue: 3
Pages: 833-843
ISSN: 0950-382X (ISSN-L)
1365-2958
DOI: 10.1046/j.1365-2958.2003.03474.x
PMC: PMC1992516
OpenAlex: W2120842435
Cited by: 712
References: 61
Citations by year: 2026: 20 · 2025: 22 · 2024: 20 · 2023: 26 · 2022: 24 · 2021: 37 · 2020: 34 · 2019: 35 · 2018: 28 · 2017: 33 · 2016: 30 · 2015: 31 · 2014: 46 · 2013: 32 · 2012: 41
FWCI: 14.66
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Molecular Microbiology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Science Foundation (9974498)
National Institutes of Health
National Human Genome Research Institute (HG02602-01, R01HG002602)
National Institute of Allergy and Infectious Diseases (R01AI044826, AI-44826, R21AI047744, AI47744, R01AI047744)
Topics: Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
Keywords: Mycobacterium tuberculosis, transcription factors, hypoxia response, hypoxia, transcriptional regulation, two-component response regulator, DNA-binding motifs, alpha-crystallin, latent tuberculosis infection, gene induction
MeSH terms: Hypoxia, Aspartic Acid, Bacterial Proteins, Humans, Mycobacterium tuberculosis, Oxygen, Protein Binding, Regulatory Sequences, Nucleic Acid, Transcription Factors, Tuberculosis, Gene Expression Regulation, Bacterial, Genes, Reporter, Gene Targeting, Oligonucleotide Array Sequence Analysis

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

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