Biochemistry and Molecular Microbiology.
M. tuberculosis phoP-phoR system controls a variety of functions including stress response, respiratory metabolism, secretion of the major T-cell antigen ESAT-6, and synthesis of pathogenic lipids. Thus, a phoP disruption mutant of M. tuberculosis is significantly growth attenuated in animal models. However, the exact role of PhoP in intracellular growth of the bacilli or the basis for growth attenuation of the phoP mutant in macrophages and mice remains unknown. Our work showing PhoP phosphorylation, DNA-protein and protein-protein interactions by the regulator represent the most original contributions to our understanding on how this system impacts different aspects of M. tuberculosis physiology.
- Goyal, R., Das, A. K., Singh, R., Singh, P. K., Korpole, S., and Sarkar, D. (2011) Phosphorylation of PhoP protein plays direct regulatory role in lipid biosynthesis of Mycobacterium tuberculosis. J. Biol. Chem. 286, 45197-45208
- Das, A. K., Anil Kumar, V., Sevalkar, R. R., Bansal, R. and Sarkar, D. (2013) Unique N-terminal arm of Mycobacterium tuberculosis PhoP plays an unusual role in its regulatory function. J. Biol. Chem. 288, 29182-29192
- Singh, R., V., Anil Kumar., Das, A. K., Bansal, R. and Sarkar, D. (2014) A transcriptional co-repressor regulatory circuit controlling the heat-shock response of Mycobacterium tuberculosis. Mol. Microbiol. 94, 450-465
- Anil Kumar, V., Goyal, R., Bansal, R., Singh, N., Sevalkar, R. R., Kumar, A., and Sarkar D. (2016) EspR-dependent ESAT-6 secretion of Mycobacterium tuberculosis requires the presence of virulence regulator PhoP. J. Biol. Chem. 291, 19018-19030
- Bansal, R, Anil Kumar, V., Sevalkar, R.R., Singh, P. R., and Sarkar, D. (2017) Mycobacterium tuberculosis virulence-regulator PhoP interacts with alternative sigma factor SigE during acid-stress response. Mol. Microbiol. 104, 400-411
- Sevalkar, R. R., Arora, D., Singh, P.R., Singh, R., Nandicoori, V.K., Karthikeyan, S., and Sarkar, D. (2019) Functioning of mycobacterial heat-shock repressors requires the master virulence regulator PhoP. J Bacteriol 201, e00013-19.