title: Mycobacterium tuberculosis two-component systems and implications in novel vaccines and drugs.
abstract: Communication is vital for nearly all organisms to survive and thrive. For some particularly successful intracellular pathogens, a robust and precise signal transduction system is imperative for handling the complex, volatile, and harsh niche. The communication network of the etiology of tuberculosis, Mycobacterium tuberculosis (M.tb), namely two-component system (TCS), the eukaryotic-like Ser/Thr protein kinases(STPKs) system, the protein tyrosine kinase(PTK) system and the extracytoplasmic function σ(ECF-σ) system, determine how the pathogen responds to environmental fluctuations. At least 12 pair TCSs and four orphan proteins (three response regulators, Rv2884, Rv0260c, Rv0818, and one putative sensory transduction protein, Rv3143) can be found in the M.tb H37Rv genome. They regulate various aspects of M.tb, including virulence, dormancy, persistence, and drug resistance. This review focuses on the physiological roles of TCSs and the network of M.tb TCSs from a systems biology perspective. The implications of TCSs for better vaccine and new drug targets against tuberculosis are also examined.
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Enviroment and Bio-Resource of the Three Gorges Area, School of Life Sciences, Southwest University, Chongqing 400715, China.
authors.forename: PeiFu
authors.initials: P
authors.lastname: Zhou
authors.forename: QuanXin
authors.initials: Q
authors.lastname: Long
authors.forename: YeXin
authors.initials: Y
authors.lastname: Zhou
authors.forename: HongHai
authors.initials: H
authors.lastname: Wang
authors.forename: JianPing
authors.initials: J
authors.lastname: Xie
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D055808:Drug Discovery; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006168:Guinea Pigs; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D008253:Macaca mulatta; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism; D006656:Protamine Kinase / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014376:Tuberculosis / Q000378:metabolism*; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C542863:DosR protein, Mycobacterium tuberculosis; C509805:KIF2A protein, human; C110608:RegX3 protein, Mycobacterium; D012808:Sigma Factor; D032581:Tuberculosis Vaccines; D010770:Phosphotransferases; D011494:Protein Kinases; C472074:HK1 protein, human; D006593:Hexokinase; D011505:Protein-Tyrosine Kinases; C506260:DevS protein, Mycobacterium tuberculosis; D006656:Protamine Kinase; D017346:Protein Serine-Threonine Kinases; C542862:DosT protein, Mycobacterium tuberculosis; C110607:SenX3 protein, Mycobacterium; D006867:Hydrolases; D016547:Kinesins; C527647:HsaD protein, Mycobacterium tuberculosis