Antimicrobial resistance threatens the control of an ever-increasing range of infections. Tuberculosis (TB) alone, with an estimated 2 billion people infected across the world, has caused 1.4 million human lives every year. Many aspects of the causative agent, Mycobacterium tuberculosis, make this disease difficult for healthcare and laboratory researchers to fight against, such as unique pathophysiology, latent infection and complex treatment regimens. In this multi-disciplinary research project, we aim to investigate the immunomodulatory behaviour of drugs and a selection of newly synthesized analogues as chemical tools to decipher the molecular mechanisms of their target endogenous functions in mycobacteria.
1 Carprofen elicits pleiotropic mechanisms of bactericidal action with the potential to reverse antimicrobial drug resistance in tuberculosis. (2020) Maitra A, Evangelopoulos D, Chrzastek A, Martin LT, Hanrath A, Chapman E, Hailes HC, Lipman M, McHugh TD, Waddell SJ and Bhakta S* J Antimicrob Chemother;75(11):3194-3201. doi: 10.1093/jac/dkaa307.PMID: 32790867
2 Repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-inflammatory drugs. (2016) Maitra A, Bates S, Shaik M, Evangelopoulos D, Abubakar I, McHugh TD, Lipman M, Bhakta S*. British Medical Bulletin 118(1):138-48. doi: 10.1093/bmb/ldw019.
3 Nonsteroidal anti-inflammatory drug sensitizes Mycobacterium tuberculosis to endogenous and exogenous antimicrobials. (2012) Gold B, Pingle M, Brickner SJ, Shah N, Roberts J, Rundell M, Bracken WC, Warrier T, Somersan S, Venugopal A, Darby C, Jiang X, Warren JD, Fernandez J, Ouerfelli O, Nuermberger EL, Cunningham-Bussel A, Rath P, Chidawanyika T, Deng H, Realubit R, Glickman JF, Nathan CF. Proc Natl Acad Sci U S A. 2;109(40):16004-11. doi: 10.1073/pnas.1214188109.
4 Repurposing-a ray of hope in tackling extensively drug resistance in tuberculosis. (2015) Maitra A, Bates S, Kolvekar T, Devarajan PV, Guzman JD, Bhakta S.* Int J Infect Dis. 32:50-5. doi: 10.1016/j.ijid.2014.12.031.
5 Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay. (2013) Guzman JD, Evangelopoulos D, Gupta A, Birchall K, Mwaigwisya S, Saxty B, McHugh TD, Gibbons S, Malkinson J, Bhakta S.* BMJ Open. 20;3(6). pii: e002672. doi: 10.1136/bmjopen-2013-002672.