Profile
The laboratory's focus is on understanding novel metabolic pathways that enable bacteria to adapt to different stress conditions and in host tissues. The research work also focusses on development of novel therapeutics and vaccine candidates against TB.
Current Focus Areas
We have successfully shown that the fine regulation of the relative levels of toxins and antitoxins is essential for M. tuberculosis to establish infection in the host tissues. We have also performed structural studies to determine the interactions between cognate and non-cognate TA systems.
We have functionally characterized enzymes involved in inorganic polyphosphate metabolism. We show that PolyP homeostasis is essential for M. tuberculosis to establish infection in vivo. Using a combination of cutting-edge tools, his group has shown that PolyP levels regulate tolerance to drugs and expression of virulence associated genes.
The extensive work being performed in the laboratory has led to the identification of novel vaccine candidates that impart protection in pre-clinical animal models. In preclinical animal models, immunization with these vaccine candidates results in the induction of TH1 and activated memory immune response.
Another dimension of the research program is the development and application of target-based, phenotypic based and macrophage-based screens to identify small molecules that are active against both drug-resistant and drug-sensitive bacteria. The identified molecules possess a novel mechanism of action and also inhibit the growth of intracellular bacteria.
Selected Publications
1. Gosain TP, Chugh S, Rizvi ZA, Chauhan NK, Kidwai S, Thakur KG, Awasthi A and Singh R*. Mycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs. Nature Communications, 2024,15:5467. 2. Chugh S, Tiwari P, Suri C, Gupta SK, Singh P, Bouzeyne R, Kidwai S, Srivastava M, Rameshwaram NR, Kumar Y, Asthana S and Singh R*. Polyphosphate Kinase -1 regulates bacterial and host metabolic pathways involved in pathogenesis of Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences, 2024, 121(2), e2309664121. 3. Agarwal S, Sharma A, Bouzeyen R, Deep A, Sharma H, Mangalaparthu K, Datta KK, Kidwai S, Gowda H, Varadarajan R, Sharma RD, Thakur KG and Singh R. VapBC22 toxin-antitoxin system from Mycobacterium tuberculosis is required for pathogenesis and modulation of host immune response. Science Advances 2020, 1-15. 4. Tiwari P, Arora G, Singh M, Kidwai S, Narayan O, and Singh R. MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs. Nature Communications 6(1), 2015, 1-13. 5. Deep A, Tiwari P, Agarwal S, Kaundal S, Kidwai S, Singh R*, and Thakur KG*. Structural, functional and biological insights into the role of Mycobacterium tuberculosis VapBC11 toxin-antitoxin system: targeting a tRNase to tackle mycobacterial adaptation. Nucleic acids Research 21, 2018, 11639-11655. *co-corresponding author.