Transcriptomics

Dataset Information

40

The unique roles of DosT and DosS in DosR regulon induction and Mycobacterium tuberculosis dormancy


ABSTRACT: In Mycobacterium tuberculosis, the sensor kinases DosT and DosS activate the transcriptional regulator DosR, resulting in the induction of the DosR regulon, important for anaerobic survival and perhaps latent infection. The individual and collective roles of these sensors has been postulated biochemically, but their roles have remained unclear in vivo. This work demonstrates distinct and additive roles for each sensor during anaerobic dormancy. Both sensors are necessary for wild type levels of DosR regulon induction, and concomitantly, full induction of the regulon is required for wild type anaerobic survival. In the anaerobic model, DosT plays an early role, responding to hypoxia. DosT then induces the regulon and with it DosS, which sustains and further induces the regulon. DosT then loses its functionality as oxygen becomes limited, and DosS alone maintains induction of the genes from that point forward. Thus, M. tuberculosis has evolved a system whereby it responds to hypoxic conditions in a stepwise fashion as it enters an anaerobic state. Overall design: Various DosS and DosT mutant strains were analyzed against wild type (reference strain H37Rv, identical conditions as mutant) under various conditions: day 6 in an anaerobic dormancy model, 4 or 24 hours in a GasPak model, or log phase with the addition of a nitric oxide donor. Experiments were repeated in triplicate or quadruplicate.

INSTRUMENT(S): Univ Colorado Denver Mycobacterium tuberculosis 4.6K Operon Microarray

ORGANISM(S): Mycobacterium tuberculosis H37Rv  

SUBMITTER: Ryan William Honaker 

PROVIDER: GSE16811 | GEO | 2009-06-26

SECONDARY ACCESSION(S): PRJNA117523

REPOSITORIES: GEO

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