About the lab
The Mycobacteria Research Laboratory is proactively engaged in an integrated interdisciplinary research programme for accelerating antimicrobial drug discovery and development against tuberculosis (TB) and non-tuberculous mycobacterial (NTM) infection with a strong link to industry partners.
Mycobacteria Research Laboratory (ISMB-MRL on Twitter/X@ismb_s), a part of the Institute of Structural and Molecular Biology (ISMB) and the UCL WHO Collaborating Centre on TB Research and Innovation (UCL-TB), hosts specialized state-of-the-art microbiology and molecular biology laboratories enabling discovery research with a panel of clinically relevant mycobacterial spp. including Mycobacterium abscessus, M. marinum, M. bovis and M. tuberculosis.
We have significantly contributed to the thematic area of validation of therapeutic targets identified in tubercle and non-tuberculous mycobacteria. We are for comprehensive bioassay-guided evaluation of the novel chemical entities and their structural analogues, primarily includes: (a) whole-cell phenotypic evaluation including viability, growth and morphology against a panel of mycobacterial strains including their drug-resistant mutants in vitro to an intracellular infection model; (b) eukaryotic cell toxicity against macrophage cell lines; (c) assaying the whole-cell drug efflux inhibition and associated biofilm-disrupting properties relevant to the long-term development of the designed inhibitors.
Our predominant interest is the study of enzymes performing essential/ conditionally vital functions in mycobacterial cell wall peptidoglycan metabolism and recycling. We have also established in vitro, ex vivo whole-cell methods and models for evaluating natural products, synthetic inhibitors and over-the-counter medicines at different physiological states of a panel of WHO-priority bacterial pathogens. Through our initiatives, several small molecule hits have been discovered so far and they constitute scaffolds for generating more potent anti-infective drug leads. Our research group is leading the investigation on the potential repurposing of NSAIDs-Carprofen (Carbazole) in the development of improved adjunctive chemotherapy against TB.
Routinely, in our lab, we grow, maintain and investigate both fast- and slow-growing mycobacterial species, a number of Gram +ve and Gram -ve bacterial strains and their mutants, in our specialised GM microbiology laboratories within the state-of-the-art research unit.
Public engagement, outreach, knowledge exchange, and research skills training are an integral part of the academic research cooperation of Mycobacteria Research Laboratory through various forms of partnership agreements (MTA, CDA, MoU, MoA) in place.
Contact us
Professor Sanjib Bhakta (Academic Head of Laboratory and Professor of Molecular Microbiology and Biochemistry)
Our key publications
- Here is a selection of some of our publications:
- Characterization of the MurT/GatD complex in Mycobacterium tuberculosis towards validating a novel anti-tubercular drug target. (2021) Maitra A, Nukala S, Dickman R, Martin LT, Munshi T, Gupta A, Shepherd AJ, Arnvig KB, Tabor AB, Keep NH, Bhakta S.* J Antimicrob Chemother: Antimicrob Resist;3(1):dlab028. doi: 10.1093/jacamr/dlab028
- New InhA Inhibitors Based on Expanded Triclosan and Di-Triclosan Analogues to Develop a New Treatment for Tuberculosis. (2021) Chetty S, Armstrong T, Sharma Kharkwal S, Drewe WC, De Matteis CI, Evangelopoulos D, Bhakta S., Thomas NR. Pharmaceuticals (Basel);14(4):361. doi: 10.3390/ph14040361
- The Mycobactin Biosynthesis Pathway: A Prospective Therapeutic Target in the Battle against Tuberculosis. (2021) Shyam M, Shilkar D, Verma H, Dev A, Sinha BN, Brucoli F, Bhakta S., Jayaprakash V. J Med Chem. ;64(1):71-100. doi: 10.1021/acs.jmedchem.0c01176
- Weighted Gene Co-Expression Network Analysis Identifies Key Modules and Hub Genes Associated with Mycobacterial Infection of Human Macrophages. (2021) Lu L, Wei R, Bhakta S, Waddell SJ, Boix E. Antibiotics (Basel); 10(2):97. doi: 10.3390/antibiotics10020097
- 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, Bhakta S.* J Antimicrob Chemother.;75(11):3194-3201. doi: 10.1093/jac/dkaa307
- Cell wall peptidoglycan in Mycobacterium tuberculosis: An Achilles' heel for the TB-causing pathogen. (2019) Maitra A, Munshi T, Healy J, Martin LT, Vollmer W, Keep NH, Bhakta S.* FEMS Microbiol Rev.;43(5):548-575. doi: 10.1093/femsre/fuz016
- Integrated Target-Based and Phenotypic Screening Approaches for the Identification of Anti-Tubercular Agents That Bind to the Mycobacterial Adenylating Enzyme MbtA. (2019) Ferguson L, Wells G, Bhakta S, Johnson J, Guzman J, Parish T, Prentice RA, Brucoli F. ChemMedChem.;14(19):1735-1741. doi: 10.1002/cmdc.201900217
- Analogues of Disulfides from Allium stipitatum demonstrate potent anti-tubercular activities through drug efflux pump and biofilm inhibition. (2018) CA Danquah, E Kakagianni, P Khondkar, A Maitra, M Rahman, ...Bhakta, S. Nature Scientific reports 8 (1), 1150.
- Novel indole-thiazolidinone conjugates: Design, synthesis and whole-cell phenotypic evaluation as a novel class of antimicrobial agents. (2018) Abo-Ashour MF, Eldehna WM, George RF, Abdel-Aziz MM, Elaasser MM, Abdel Gawad NM, Gupta A, Bhakta S., Abou-Seri SM. Eur J Med Chem.;160:49-60. doi: 10.1016/j.ejmech.2018.10.008
- Nano-Formulation of Ethambutol with Multifunctional Graphene Oxide and Magnetic Nanoparticles Retains Its Anti-Tubercular Activity with Prospects of Improving Chemotherapeutic Efficacy. (2017) Saifullah B, Maitra A, Chrzastek A, Naeemullah B, Fakurazi S, Bhakta S, Hussein MZ. Molecules; 22(10):1697. doi: 10.3390/molecules22101697
- HT‐SPOTi: a rapid drug susceptibility test (DST) to evaluate antibiotic resistance profiles and novel chemicals for anti‐infective drug discovery. (2016) Danquah, C.A.; Maitra, A., Gibbons, S., Faull, J and Bhakta, S. Current Protocols in Microbiology 40 (1), 17.8. 1-17.8. 12
- Design and Synthesis of 1-((1,5-Bis(4-chlorophenyl)-2-methyl-1H-pyrrol-3-yl)methyl)-4-methylpiperazine (BM212) and N-Adamantan-2-yl-N′-((E)-3,7 ... (2016) Bhakta, S., Scalacci, N., Maitra, A., Brown, A.K., Dasugari, S., Evangelopoulos, D. ... Journal of Medicinal Chemistry 59 (6), 2780-2793.
- Tetrahydroisoquinolines affect the whole-cell phenotype of Mycobacterium tuberculosis by inhibiting the ATP-dependent MurE ligase. (2015) Guzman JD, Pesnot T, Barrera DA, Davies HM, McMahon E, Evangelopoulos D, Mortazavi PN, Munshi T, Maitra A, Lamming ED, Angell R, Gershater MC, Redmond JM, Needham D, Ward JM, Cuca LE, Hailes HC, Bhakta S.* J Antimicrob Chemother.;70(6):1691-703. doi: 10.1093/jac/dkv010
- Characterisation of a putative AraC transcriptional regulator from Mycobacterium smegmatis. (2014) Evangelopoulos D, Gupta A, Lack NA, Maitra A, ten Bokum AM, Kendall S, Sim E, Bhakta S.* Tuberculosis; 94(6):664-71. doi: 10.1016/j.tube.2014.08.007
- Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay. (2013) JD Guzman, D Evangelopoulos, A Gupta, K Birchall, S Mwaigwisya, ... Bhakta, S. BMJ open 3 (6), e002672.
- Characterisation of ATP-dependent Mur ligases involved in the biogenesis of cell wall peptidoglycan in Mycobacterium tuberculosis (2013) Munshi, T., Gupta, A., Evangelopoulos, D., Guzman, J.D., Gibbons, S., Keep, N.H. and Bhakta, S. PloS one 8 (3), e60143
- An integrated surrogate model for screening of drugs against Mycobacterium tuberculosis Gupta, A. and Bhakta, S. (2012) Journal of Antimicrobial Chemotherapy 67 (6), 1380-1391.
- Mycobacterium tuberculosis: immune evasion, latency and reactivation. (2012) Gupta A, Kaul A, Tsolaki AG, Kishore U, Bhakta S.* Immunobiology.;217(3):363-74. doi: 10.1016/j.imbio.2011.07.008
- Interaction of N-methyl-2-alkenyl-4-quinolones with ATP-dependent MurE ligase of Mycobacterium tuberculosis: antibacterial activity, molecular docking and... (2011) JD Guzman, A Wube, D Evangelopoulos, A Gupta, A Hüfner, ...Bhakta, S. Journal of Antimicrobial Chemotherapy 66 (8), 1766-1772.
- Characterization of an oxidoreductase from the arylamine N-acetyltransferase operon in Mycobacterium smegmatis. (2011) Evangelopoulos D, Cronin N, Daviter T, Sim E, Keep NH, Bhakta S.* FEBS J.;278(24):4824-32. doi: 10.1111/j.1742-4658.2011.08382.x
- Anti-tubercular screening of natural products from Colombian plants: 3-methoxynordomesticine, an inhibitor of MurE ligase of Mycobacterium tuberculosis. (2010) JD Guzman, A Gupta, D Evangelopoulos, C Basavannacharya, LC Pabon, ...Bhakta, S.
Journal of Antimicrobial Chemotherapy 65 (10), 2101-2107. - Essential residues for the enzyme activity of ATP-dependent MurE ligase from Mycobacterium tuberculosis. (2010) Basavannacharya C, Moody PR, Munshi T, Cronin N, Keep NH, Bhakta S.* Protein Cell.;1(11):1011-22. doi: 10.1007/s13238-010-0132-9
- ATP-dependent MurE ligase in Mycobacterium tuberculosis: biochemical and structural characterisation (2010) Basavannacharya, C, Robertson, G, Munshi, T, Keep, NH, Bhakta, S, Tuberculosis, 90, (1) 16-24.
- Characterization of the putative operon containing arylamine N-acetyltransferase (nat) in Mycobacterium bovis BCG. (2006) Anderton MC, Bhakta S, Besra GS, Jeavons P, Eltis LD, Sim E. Mol Microbiol.; 59(1):181-92. doi: 10.1111/j.1365-2958.2005.04945.x
- Arylamine N-acetyltransferase is required for synthesis of mycolic acids and complex lipids in Mycobacterium bovis BCG and represents a novel drug target. (2004) Bhakta, S., Besra, G.S., Upton, A.M., Parish, T., Sholto-Douglas-Vernon, C. ... Sim, E. Journal of Experimental Medicine 199 (9), 1191-1199.