The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Rv3133c/ dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis
Open accessAbstract
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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“DosR has been shown to act as a transcriptional regulator, which is responsible for the induction of nearly all hypoxia-induced genes of M. tuberculosis (96).”
From Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria (2014) · cites this paper as [96]
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Inhibition of Respiration by Nitric Oxide Induces a Mycobacterium tuberculosis Dormancy Program
Voskuil, M. I., Schnappinger, D., Visconti, K. C., Harrell, M. I., Dolganov, G., Sherman, D. R., & Schoolnik, G. K. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030205 · Cited by 975
Self-citationMycobacterium tuberculosis: success through dormancy
Gengenbacher, M., & Kaufmann, S. H. E. (2012) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2012.00331.x · Cited by 722
Virulence factors of the Mycobacterium tuberculosis complex
Forrellad, M. A., Klepp, L. I., Gioffré, A., y García, J. S., Morbidoni, H. R., Santangelo, M. D. L. P., Cataldi, A. A., & Bigi, F. (2013) · Virulence · doi:10.4161/viru.22329 · Cited by 676
The immunological life cycle of tuberculosis
Ernst, J. (2012) · Nature reviews. Immunology · doi:10.1038/nri3259 · Cited by 598
Rao, S. P. S., Alonso, S., Rand, L., Dick, T., & Pethe, K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711697105 · Cited by 517
Metadata
- 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.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2003-04-09
- Volume
- 48
- Issue
- 3
- Pages
- 833-843
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- 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
- 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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