Special Section: Tuberculosis

Two-component systems and eukaryotic-like Ser/Thr protein kinases comprise major components of the signal transduction machinery of Mycobacterium tuberculosis. The elucidation of its genome sequence provided a tremendous fillip to their study. Multiple approaches embracing bioinformatics, genetics, biochemistry, cell and molecular biology and animal models are being used to characterize them and to decipher their role in the pathobiology of M. tuberculosis. Several response regulator proteins have been implicated in the survival, multiplication and persistence of M. tuberculosis in animals and cell models of virulence. Six additional mycobacterial genome sequencing projects are at advanced stages of completion. Bioinformatics tools have revealed that the two-component systems, eukaryotic-like Ser/Thr protein kinases and phosphatases are conserved to varying extents in different mycobacteria. This information will provide a jumpstart to their functional analysis. One of the best understood systems among the signal transduction proteins is the DevR– DevS two-component system. Studies from several laboratories have contributed to our present understanding of its role in the hypoxia response of pathogenic and non pathogenic mycobacteria. The current status of our knowledge of this and other signal transduction systems in mycobacteria is the subject of this review.