July 2017 ARTICLE LIST >>
PharmaTutor (July - 2017)
ISSN: 2347 - 7881
(Volume 5, Issue 7)
Received On: 16/03/2017; Accepted On: 22/03/2017; Published On: 01/07/2017
AUTHORS:
Amiya Kumar Ghosh*1,Saptarshi Samajdar2, Shiladitya Palit3, Rupchand Pandit4
1Department of Pharmaceutical Technology,
Utkal University, Bhubaneswar, Odisha, India.
2Centre for Pharmaceutical Sciences and Natural Products,
Central University of Punjab, Bathinda, Punjab, India
3Department of Pharmaceutics, IITBHU, Varanasi, India
4Department of Pharmaceutical Science & Technology,
Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India
*amiyaghosh94@gmail.com
ABSTRACT:
Tuberculosis (TB) has been declared as a global health emergency by the World Health Organization(WHO). This has been mainly due to the emergence of multiple drug resistant strains and the synergy between tubercle bacilli and the human immunodeficiency virus (HIV). Mycobacterium tuberculosis (Mtb) is a pathogenic bacteria species in the genus Mycobacterium and the causative agent of most cases of tuberculosis. Tuberculosis (TB) is the leading cause of death in the world from a bacterial infectious disease. This antibiotic resistance strain lead to development of the new antibiotics or drug molecules which can kill or suppress the growth of Mycobacterium tuberculosis.The need for new antiTB is persistent due to the emergence of drug resistant Mycobacterium tuberculosis. Here we aimto identify new drug targets in Mycobacterium tuberculosis by phylogenomics among the Mycobacterium tuberculosisandcomparative genomics to Homo sapiens. The proposed target discovery pipeline is largely independent of experimental data and based on the assumption that Mycobacterium tuberculosis proteins are likely to be essential if (i) there are no similar proteins in the same proteome and (ii) they are highly conserved across the Mycobacterium tuberculosisof mammals. We have performed an in silicocomparative analysis of metabolic pathways of the host Homo sapiens and the pathogen Mycobacterium tuberculosis (H37Rv). Novel efforts in developing drugs that target the intracellular metabolismof M. tuberculosis often focus on metabolic pathways that are specific to M. tuberculosis. We have identified five unique pathwaysfor Mycobacterium tuberculosis having a number of 60 enzymes, which are nonhomologous to Homo sapiens protein sequences,and among them there were 55 enzymes, which are nonhomologous to Homo sapiens protein sequences.These enzymes were alsofound to be essential for survival of theMycobacteriumtuberculosisaccording to the DEG database. Further, the functional analysis using Uniprot showed involvement of all the unique enzymes in the different cellular components.
How to cite this article: Ghosh AK, Samajdar S, Palit S, Pandit R;Drug targets identification of Mycobacterium tuberculosis by metabolic pathway analysis: insilico process; PharmaTutor; 2017; 5(7); 43-53
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REFERENCES:
1. Sharma SK, Mohan V. Multidrug-resistant tuberculosis.Indian J Med Res 2004; 120 : 354-76.
2. Chakhaiyar P, Hasnain SE. Defining the mandate oftuberculosis research in a post genomic era. Med Princ Prac2004; 13 : 177-84.
3. S. H. E. Kaufmann, “Envisioning future strategies for vaccination against tuberculosis,” Nature Reviews Immunology, vol. 6, no. 9, pp. 699–704, 2006.
4. B. Greenwood, “Aglobal actionplan for the preventionandcontrol of pneumonia,” Bulletin of the World Health Organization, vol. 86, no. 5, p. 322, 2008.
5. P. Nunn, B. Williams, K. Floyd, C. Dye, G. Elzinga, and M. Raviglione, “Tuberculosis control in the era of HIV,” Nature Reviews Immunology, vol. 5, no. 10, pp. 819–826, 2005.
6. Siddiqi N, Shamim M, Hussain S, Choudhary RK, Ahmed N, Prachee, et al. Molecular characterization of multidrugresistant isolates of Mycobacterium tuberculosis from patients in north India. Antimicrob Agents Chemother 2002;46 : 443-50.
7.Siddiqi N, Das R, Pathak N, Banerjee S, Ahmed N, Katoch VM, et al. Mycobacterium tuberculosis isolate witha distinct genomic identity overexpresses a TAP like efflux pump. Infection 2004; 32 : 109-11.
8. Majid AA, Ahmed N, Rao KR, Ghousunnissa S, Kausar F, Bose B, et al. AmpliBASE MT: A Mycobacteriumtuberculosis diversity knowledgebase. Bioinformatics 2002;20: 989-92.
9.A.M. Feist andB. Palsson, “Thegrowing scopeof applicationsof genome-scale metabolic reconstructions using Escherichia coli,” Nature Biotechnology, vol. 26, no. 6, pp. 659–667, 2008.
10. A. Dutta, S. K. Singh, P. Ghosh, R. Mukherjee, S. Mitter, and D. Bandyopadhyay, “In silico identification of potential therapeutic targets in the human pathogen Helicobacter pylori,” InSilico Biology, vol. 6, no. 1-2, pp. 43–47, 2006.
11. O. Ates, E. T. Oner, and K. Y. Arga, “Genome-scale reconstruction of metabolic network for a halophilic extremophile, Chromohalobacter salexigens DSM3043,” BMC Systems Biology, vol. 5, article 12, 2011.
12.A. Raghunathan, J. Reed, S. Shin, B. Palsson, and S. Daefler, “Constraint-based analysis of metabolic capacity of Salmonellatyphimurium during host-pathogen interaction,” BMC SystemsBiology, vol. 3, article 38, 2009.
13.A. M. Feist, C. S. Henry, J. L. Reed et al., “A genome-scale metabolic reconstruction for Escherichia coli K-12MG1655 that accounts for 1260 ORFs and thermodynamic information,” Molecular Systems Biology, vol. 3, article 121, 2007.
14. N. C. Duarte, M. J. Herrg˚ard, and B. Ø. Palsson, “Reconstruction and validation of Saccharomyces cerevisiae iND750, a fully compartmentalized genome-scale metabolic model,” GenomeResearch, vol. 14, no. 7, pp. 1298–1309, 2004.
15.A. K. Chavali, J.D.Whittemore, J. A. Eddy, K. T.Williams, and J. A. Papin, “Systems analysis of metabolism in the pathogenic trypanosomatid Leishmania major,” Molecular Systems Biology, vol. 4, article 177, 2008.
16. K. R. Sakharkar, M. K. Sakharkar, and V. T. K. Chow, “A novel genomics approach for the identification of drug targets in pathogens, with special reference to Pseudomonas aeruginosa,”
In Silico Biology, vol. 4, no. 3, pp. 355–360, 2004.
17. M. Y. Galperin and E. V. Koonin, “Searching for drug targets in microbial genomes,” Current Opinion in Biotechnology, vol. 10, no. 6, pp. 571–578, 1999.
18.M. Kanehisa, S. Goto, S. Kawashima, and A. Nakaya, “Thed KEGG databases at GenomeNet,” Nucleic Acids Research, vol. 30, no. 1, pp. 42–46, 2002.
19. R. Zhang, H.-Y. Ou, and C.-T. Zhang, “DEG: a database of essential genes,” Nucleic Acids Research, vol. 32, pp. D271–D272, 2004.