title: The Mycobacterium tuberculosis DosR regulon assists in metabolic homeostasis and enables rapid recovery from nonrespiring dormancy.
abstract: Mycobacterium tuberculosis survives in latently infected individuals, likely in a nonreplicating or dormancy-like state. The M. tuberculosis DosR regulon is a genetic program induced by conditions that inhibit aerobic respiration and prevent bacillus replication. In this study, we used a mutant incapable of DosR regulon induction to investigate the contribution of this regulon to bacterial metabolism during anaerobic dormancy. Our results confirm that the DosR regulon is essential for M. tuberculosis survival during anaerobic dormancy and demonstrate that it is required for metabolic processes that occur upon entry into and throughout the dormant state. Specifically, we showed that regulon mechanisms shift metabolism away from aerobic respiration in the face of dwindling oxygen availability and are required for maintaining energy levels and redox balance as the culture becomes anaerobic. We also demonstrated that the DosR regulon is crucial for rapid resumption of growth once M. tuberculosis exits an anaerobic or nitric oxide-induced nonrespiring state. In summary, the DosR regulon encodes novel metabolic mechanisms essential for M. tuberculosis to survive in the absence of respiration and to successfully transition rapidly between respiring and nonrespiring conditions without loss of viability.
authors.affiliation: University of Colorado Denver, School of Medicine, Department of Microbiology, P18-9115, 12800 East 19th Avenue, PO Box 6511, Aurora, CO 80045, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Leistikow
authors.forename: Russell A
authors.initials: RA
authors.lastname: Morton
authors.forename: Iona L
authors.initials: IL
authors.lastname: Bartek
authors.forename: Isaac
authors.initials: I
authors.lastname: Frimpong
authors.forename: Karleen
authors.initials: K
authors.lastname: Wagner
authors.forename: Martin I
authors.initials: MI
authors.lastname: Voskuil
mesh_terms: D000693:Anaerobiosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D050296:Microbial Viability; D009154:Mutation; D009169:Mycobacterium tuberculosis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C542863:DosR protein, Mycobacterium tuberculosis; D011494:Protein Kinases