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- Title
Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis.
- Authors
Park, Heui-Dong; Guinn, Kristi M; Harrell, Maria I; Liao, Reiling; Voskuil, Martin I; Tompa, Martin; Schoolnik, Gary K; Sherman, David R
- 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.
- Publication
Molecular microbiology, 2003, Vol 48, Issue 3, p833
- ISSN
0950-382X
- Publication type
Journal Article
- DOI
10.1046/j.1365-2958.2003.03474.x