Two‐Component Systems, Protein Kinases, and Signal Transduction in Mycobacterium tuberculosis

Abstract

This chapter covers two types of regulatory signal transduction elements in Mycobacterium tuberculosis: (i) histidine protein kinase response regulators, referred to as two-component systems, and (ii) eucaryotic-type Ser/Thr protein kinases (STPKs). The chapter is divided into two parts, covering the two types of phosphotransfer signaling systems individually. The prototypical two-component systems consist of a histidine protein kinase (often functioning as an environmental sensor), which, as a manifestation of signal transduction, phosphorylates an aspartate residue on its cognate response regulator (a transcriptional regulator or a regulator of other proteins). The observations that inactivation of five different two-component systems increases the ability of M. tuberculosis to kill the murine host or enhances the growth of the mutant strains in mice or macrophages may reflect evolutionary adaptations of M. tuberculosis important for propagation and infectious cycle of the pathogen. Protein phosphorylation is carried out by specific protein kinases and is coupled to dephosphorylation reactions carried out by protein phosphatases. The eukaryotic protein kinases and phosphatases form the backbone of this signal transduction pathway. M. tuberculosis encodes and expresses at least eight eukaryotic-like protein kinases, and six proteins can be phosphorylated in vitro, suggesting the presence of functional kinases in M. tuberculosis. Interference with the normal immune response of the host during mycobacterial infection could be mediated by disabling host signaling pathways.