title: 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, which is important for anaerobic survival and perhaps latent infection. The individual and collective roles of these sensors have been postulated biochemically, but their roles in vivo have remained unclear. 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.
authors.affiliation: University of Colorado Denver, Department of Microbiology, Aurora, CO 80045, USA.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Honaker
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Leistikow
authors.forename: Iona L
authors.initials: IL
authors.lastname: Bartek
authors.forename: Martin I
authors.initials: MI
authors.lastname: Voskuil
mesh_terms: D000693:Anaerobiosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D006656:Protamine Kinase / Q000235:genetics / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism*; D018085:Regulon; D013312:Stress, Physiological
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C542863:DosR protein, Mycobacterium tuberculosis; D011494:Protein Kinases; C506260:DevS protein, Mycobacterium tuberculosis; D006656:Protamine Kinase; C542862:DosT protein, Mycobacterium tuberculosis