http://dkr.cdri.res.in:8080/xmlui/handle/123456789/486 2026-04-19T13:40:35Z http://dkr.cdri.res.in:8080/xmlui/handle/1/1705 Cofactor Biosynthetic Pathways in Mycobacterium tuberculosisas Potential Drug Targets Pandey, Shilpika; Gaur, Sarthak; Topno, Neha; Chopra, Sidharth; Dasgupta, Arunava There are many chemotherapeutic interventions available for tuberculosis (TB) and are in use for more than five decades, but still there is an urgent need for novel drugs against new targets due to emergence of resistant strains. Moreover, the ability of Mycobacterium tuberculosis(Mtb) to survive within granulomas in a non-replicating latent stage prolongs the course of drug dose and hence increases the severity of the disease. The significant rerouting of metabolism is one of the key processes that help mycobacteria adapt to the hostile environment of host granuloma. In this review, we are focusing on some of the cofactor biosynthetic pathways of Mycobacterium tuberculosisand their utilization as drug targets. 2014-01-01T00:00:00Z http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1682 Eravacycline: A Monograph Chopra, Sidharth; Dasgupta, Arunava Eravacycline (TP-434) is a novel and fully synthetic, broad spectrum IV/oral antibiotic for treatment of complicated urinary tract infections and complicated intra-abdominal infections caused by multi-drug resistant Gram-negative and Gram-positive bacteria, anaerobic and atypical pathogens. Eravacycline is active against strains expressing all major mechanisms of antibiotic resistance to bacterial protein translation inhibitors, including tetracycline-specific efflux and ribosomal protection mechanisms. Furthermore, it is demonstrated greater potency in comparison to currently marketed antibiotics in clinical trials. It has recently gained qualified infectious disease product designation from FDA in 2013 for the treatment of complicated Intra-abdominal infection and complicated urinary tract infection. 2014-01-01T00:00:00Z http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1448 Current approaches for new TB drugs Pandey, Shilpika; Soni, Isha; Topno, Neha; Dasgupta, Arunava; Chopra, Sidharth Tuberculosis is essentially a curable disease but inspite of a WHO approved DOTS therapy, it still continues to ravage mankind. This situation is exacerbated by long course of chemotherapy, increasing drug resistance and co-emergence with HIV. The TB drug pipeline remained stagnant for a long time with no new drug approved till FDA approval for Bedaquiline. This situation has now improved with a number of agents in pre-clinical and clinical development against M. tuberculosis. In this review, we are focusing on some of the newer drugs in discovery and preclinical development against M. tuberculosis. 2014-01-01T00:00:00Z http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1444 Phosphorylation of Pyruvate Kinase A by Protein Kinase J leads to the altered growth and differential rate of intracellular survival of mycobacteria Singh, D K; Singh, P K; Tiwari, Sameer; Singh, S K; Kumari, Ruma; Tripathi, D K; Srivastava, K K PknJ (Rv2088) is a serine / threonine protein kinase of mycobacteria which is present in Mycobacterium tuberculosis (MTB) but its gene is absent in Mycobacterium smegmatis (MS), a fast grower and non-pathogenic species of mycobacteria. The heterologous expression of MTB specific PknJ in MS altered the growth of recombinant mycobacteria highlighting one of the characteristics of this protein. This nature of the protein was further confirmed when M. bovis BCG (BCG) containing anti-sense copy of pknJ resulted in the increased growth of BCG. The real time RNA quantification analyses pointed out towards increased expression of this protein during infection of THP-1 macrophage cells which further emphasized that the protein is essential for the intracellular survival of mycobacteria. The differential in gel electrophoresis (DIGE) data followed by mass spectroscopy suggested that PknJ is involved in regulation of Pyruvate Kinase A (Rv1617). Since Pyruvate Kinase A (PK) is one of the key enzymes which controls glycolytic cycle in mycobacteria, we looked for its interaction with PknJ during extracellular and intracellular growth of mycobacteria. In order to identify the specific residue(s) involved in post-translational modification, the phospho-null mutants of PK were generated and their substrate specificities in response to PknJ were assessed through kinase assay. The findings thus underlined that the PK activity is predominantly dependent on the threonine residue at the 94th position and further suggested that this site may be plausible in intracellular survival of mycobacteria upon phosphorylation with PknJ 2014-01-01T00:00:00Z