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.
- 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.
- Singh, P.R., Anil Kumar, V., and Sarkar, D. (2020) Metabolic switching of Mycobacterium tuberculosis during hypoxia is controlled by the virulence regulator PhoP. J Bacteriol 202, e00705-19.
- Goar, H., Paul, P., Khan, H., and Sarkar, D. (2022) Molecular connectivity between extracytoplasmic sigma factors and PhoP accounts for coupled mycobacterial stress response. J Bacteriol 204, 10.1128/jb.e00110-22.
- Khan, H., Paul, P., Sevalkar, R.R., Kachhap, S., Singh, B., Sarkar, D. (2022) Convergence of two global regulators to coordinate expression of essential virulence determinants of Mycobacterium tuberculosis. eLife 2022; 11: e80965