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BSc (Hons), MSc, PhD (Bose Institute), DPhil (Oxford), PGCHE (London)
University Senior Lecturer in Microbiology
Fellow of the Higher Education Academy, UK
Head of Mycobacteria Research Laboratory
Microbiology Unit, Institute of Structural and Molecular Biology
Department of Biological Sciences
Birkbeck, University of London
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Honorary Lecturer
UCL School of Life and Medical Sciences
University College London
&
Affiliated Academic Member
Centre for Infection, Immunity and Disease Mechanisms
Brunel University, West London
Research interests
More than 9.3 million new cases and 1.8 million deaths were notified globally in 2008 according to the latest WHO Report. As many as 50 million people, worldwide are currently infected with Multiple Drug Resistant TB and 20 million people are predicted to die from TB before the end of this decade. A concerted global effort to tackle Tuberculosis (TB) is a health emergency.
Mycobacterium tuberculosis, is a member of the order Actinomycetales, causes TB. The order Actinomycetales includes other pathogens, such as Mycobacterium leprae, Mycobacterium avium, Mycobacterium marinum and Mycobacterium bovis. These pathogens are major concerns in both human and animal (birds, fish, and cattle) health. There are also many biotechnologically significant genera amongst the Actinomycetales involved in the production of antibiotics (Streptomyces, Actinomyces), production of amino acids (Corynebacterium glutamicum), used in the bioremediation of various petroleum products, di-n-butyl phthalate, benzene, toluene, m-xylene (BTX), their mixtures and styrene gas (Rhodococcus spp.), fixation of atmospheric nitrogen (Frankia spp.).
A key common feature of these related genera are their complex cell walls, which consist of an unusual mycolyl-arabinogalactan-peptidoglycan complex. Research interests in my laboratory is focused on understanding the basic cell wall physiology of this group of microorganisms towards evaluating therapeutic approaches for combating diseases.
Research outlines: Structure, function and regulation of key enzymes in cell wall peptidoglycan biosynthetic pathways to identify novel therapeutic targets in mycobacteria; understanding molecular mechanisms of persistence and drug resistance in mycobacteria; developing high throughput models for biological evaluation of anti-mycobacterials.
Publications
1. Gupta, A. and Bhakta, S. (2012) An integrated surrogate model for screening of drugs against Mycobacterium tuberculosis. J. Antimicrob. Chemotherapy (accepted in press)
2. Markarian, S. A., Harutyunyan, L.R., Pepoyan, E.K., Evangelopoulos, D., Guzman, J.D., McHugh, T.D. and Bhakta, S. (2012) The properties of mixtures of Isoniazid in water and dimethylsulfoxide J. Sol. Chemistry (accepted in press).
3. Osman,K., Evangelopoulos, D., Basavannacharya,C., Gupta, A., McHugh, T.D., Bhakta, S* and Gibbons, S.* (2012) An antibacterial from Hypericum acmosepalum inhibits ATP dependent MurE ligase from Mycobacterium tuberculosis. Int. J. Antimicrob. Agents 39(2):124-9.
4. Evangelopoulos, D., Cronin, N., Daviter, T., Sim, E., Keep, N. H. and Bhakta, S.* (2011) Characterisation of a novel oxidoreductase from the Arylamine N-acetyltransferase operon in Mycobacterium smegmatis. FEBS J. 278(24):4824-32.
5. Guzman, J. D., Wube, A., Evangelopoulos, D., Gupta, A., Hüfner, A., Basavannacharya, C., Raman, M. M., Thomaschitz, C., Bauer, R., McHugh, T. D., Nobeli, I., Prieto, J. M., Gibbons, S., Bucar, F. ¶ and Bhakta, S.¶* (2011) Interaction of N-methyl-2-alkenyl-4-quinolones with ATP-dependent MurE ligase of Mycobacterium tuberculosis: antibacterial activity, molecular docking and inhibition kinetics. J. Antimicrob. Chemotherapy 66(8):1766-72. (¶equal contribution).
6. Basavannacharya, C., Moody, P. R., Munshi, T., Cronin, N., Keep, N. H. & Bhakta, S. (2010). Essential residues for the enzyme activity of ATP-dependent MurE ligase from Mycobacterium tuberculosis. Protein & Cell 1(11), 1011-1022 (featured as cover page article)
7. Guzman, J-D, Gupta, A., Evangelopoulos, D., Basavannacharya, C., Pabon, L.C., Plazas, E.A., Muñoz, D.R., Delgado, W.A., Cuca, L.E., Ribon, W., Gibbons, S. and Bhakta, S. (2010) Anti-tubercular screening of natural products from Colombian plants: 3-5 methoxy nordomesticine, an inhibitor of MurE ligase of Mycobacterium tuberculosis. J Antimicrob. Chemotherapy (accepted, in press)
8. Basavannacharya, C.; Robertson, G.; Munshi, T.; Keep, N. and Bhakta, S. (2010) ATP-dependent MurE ligase in Mycobacterium tuberculosis: Biochemical and structural characterisation. Tuberculosis (Elsevier) 90(1):16-24.
9. Westwood I.M.†, Bhakta, S. †, Russell, A.J. †, Fullam, E., Anderton, M.C., Akane Kawamura, A., Mulvaney, A.W., Vickers, R.J., Bhowruth, V., Besra, G.S., Lalvani, A., Davies, S.G. and Sim, E. († equal first authors) (2010) Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars. Protein & Cell 1(1): 82-95
10. Gupta, A.; Bhakta, S., Kundu, S., Gupta, M., Srivastava, B. S. and Srivastava, R. (2009) Drug resistant Mycobacterium aurum: A model for high throughput anti-Tuberculosis drug screening. J Antimicrob. Chemotherapy 64(4):774-81.
11. O'Donnell G, Poeschl R, Zimhony O, Gunaratnam M, Moreira JB, Neidle S, Evangelopoulos D, Bhakta S, Malkinson JP, Boshoff HI, Lenaerts A, Gibbons S. (2008) Bioactive Pyridine-N-oxide Disulfides from Allium stipitatum. J Nat Prod. 72(3):360-365.
12. Smellie I, Bhakta S, Sim E, Fairbanks A (2007) Synthesis of putative chain terminators of mycobacterial arabinan biosynthesis. Organic and Biomolecular Chem 5 (14): 2257-66.
13. Madikane VE, Bhakta, S., Russell AJ, Campbell WE, Claridge TD, Elisha BG, Davies SG, Smith P, Sim E. (2007) Inhibition of mycobacterial arylamine N-acetyltransferase contributes to anti-mycobacterial activity of Warburgia salutaris. Bioorg Med Chem. 15(10):3579-86.
14. Anderton, M.C., Bhakta, S., Besra, G.S., Jeavons, P., Eltis, L.D. and Sim, E. (2006) Characterisation of the putative operon containing Arylamine N-acetyltransferase (nat) in Mycobacterium bovis BCG. Mol Microbiol 59(1):181-192.
15. Westwood, I.M., Holton, S.J., Rodrigues-Lima, F., Dupret, J.M., Bhakta, S., Noble, M.E., and Sim, E. (2005) Expression, purification, characterization and structure of Pseudomonas aeruginosa arylamine N-acetyltransferase. Biochem J 385: 605-612.
16. Bhakta, S., Besra, G.S., Upton, A.M., Parish, T., Sholto-Douglas-Vernon, C., Gibson, K.J., Knutton, S., Gordon, S., DaSilva, R.P., Anderton, M.C., and Sim, E. (2004) Arylamine N-acetyltransferase is required for synthesis of mycolic acids and complex lipids in Mycobacterium bovis BCG and represents a novel drug target. J Exp Med 199: 1191-1199.
17. Bhakta, S. and Basu, J. (2002) Overexpression, purification and biochemical characterization of a class A high-molecular-mass penicillin-binding protein (PBP), PBP1* and its soluble derivative from Mycobacterium tuberculosis. Biochem J 361: 635-639.
18. Choudhuri, B.S., Bhakta, S., Barik, R., Basu, J., Kundu, M., and Chakrabarti, P. (2002) Overexpression and functional characterization of an ABC (ATP-binding cassette) transporter encoded by the genes drrA and drrB of Mycobacterium tuberculosis. Biochem J 367: 279-285.
19. Datta, P., Dasgupta, A., Bhakta, S. and Basu, J. (2002) Interaction between FtsZ and FtsW of Mycobacterium tuberculosis. J Biol Chem 277: 24983-24987.
20. Mahapatra, S., Bhakta, S., Ahamed, J., and Basu, J. (2000) Characterization of derivatives of the high-molecular-mass penicillin-binding protein (PBP) 1 of Mycobacterium leprae. Biochem J 350 Pt 1: 75-80.
Review Articles:
1. Guzman, J.D.; Gupta, A.; Bucar, F.; Gibbons, S. and Bhakta, S.* (2012) Anti-mycobacterials from natural sources: ancient times, antibiotic era and novel scaffolds. Frontiers in Bioscience 17, 1861-1881.
2. Gupta, A.; Kaul, A.; Tsolaki, A.G.; Kishore, U. and Bhakta, S.* (2012) Mycobacterium tuberculosis: Immune evasion, dormancy and resuscitation. Immunobiology 217(3):363-74.
3. Sim E, Sandy J, Evangelopoulos D, Fullam E, Bhakta S, Westwood I, Krylova A, Lack N, Noble M. (2008) Arylamine N-acetyltransferases in mycobacteria. Curr Drug Metab. 9(6):510-9.
4. Sim, E., Pinter, K., Mushtaq, A., Upton, A., Sandy, J., Bhakta, S., and Noble, M. (2003) Arylamine N-acetyltransferases: a pharmacogenomic approach to drug metabolism and endogenous function. Biochem Soc Trans 31: 615-619.
Invited Public Articles:
1. Bhakta, S. (2009) Extensively drug resistant Tuberculosis (XDR-TB): cure for today or tomorrow. London Sharad Utsav Brochure, London, UK 1:1(66 - 67).
2. Bhakta, S. (2006) Tuberculosis: a big challenge whether East or the West. East-West Times, Kolkata, India 1:1(28 - 31).
Book chapter:
1. Evangelopoulos, D. and Bhakta, S.* (2010) Rapid methods for testing inhibitors of mycobacterial growth. Methods Mol Biol: Antibiotic Resistance Protocols. 642:193-201. Edited by Gillespie S.H. and McHugh T.D. Humana Press.
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