Mycobacterium tuberculosis two-component systems and implications in novel vaccines and drugs

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.