Proteome Mining for the Identification of Putative Drug Targets For Human Pathogen Clostridium Tetani

Author(s): Anum Munir, Shaukat Iqbal Malik*, Khalid Akhtar Malik.

Journal Name: Current Bioinformatics

Volume 14 , Issue 6 , 2019

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Abstract:

Background: Clostridium tetani are rod-like, anaerobic types of pathogenic bacteria of the genus Clostridium. It is Gram-positive in nature and appears as a tennis racket or drumsticks on staining with the dye. Tetanus is a neuromuscular disease wherein the Clostridium tetani exotoxin produces muscle fits in the host. Tetanus is the second leading cause of worldwide deaths occurring from the family of immunization-preventable diseases.

Methods: In this research, subtractive proteome analysis of C. tetani was performed to identify putative drug targets. The proteins were subjected to blast analysis against Homo sapiens to exclude homologous proteins. The database of Essential Genes was used to determine the essential proteins of the pathogen. These basic proteins were additionally analyzed to anticipate the corresponding metabolic pathways.

Results: Cellular localization analysis was carried out to determine the possibility of the protein presence in the outer membrane. The study has recognized 29 essential genes and 20 unique pathways of 2314 proteins as potential drug targets. There are 29 essential proteins, out of which, 3 membrane proteins were also identified as putative drug targets.

Conclusion: Virtual screening in contrast to these proteins can be valuable in the identification of novel clinical compounds for the C. tetani infections in Homo sapiens.

Keywords: Drug targets, essential genes, membrane proteins, metabolic pathways, putative, Clostridium tetani.

[1]
Cohen JE, Wang R, Shen RF, Wu WW, Keller JE. Comparative pathogenomics of Clostridium tetani. PLoS One 2017; 12(8)e0182909
[2]
Parte AC. LPSN--list of prokaryotic names with standing in nomenclature. Nucleic Acids Res 2014; 42(Database issue): D613-6.
[3]
Brüggemann H. Genomics of clostridial pathogens: implication of extrachromosomal elements in pathogenicity. Curr Opin Microbiol 2005; 8(5): 601-5.
[4]
Ndams IS, Joshua IA, Luka SA, Sadiq HO. Epidemiology of hepatitis B infection among pregnant women in Minna, Nigeria. ScientificWorldJournal 2008; 3(3)
[http://dx.doi.org/10.4314/swj.v3i3.51810]
[5]
Hallit RR, Afridi M, Sison R, Salem E, Boghossian J, Slim J. Clostridium tetani bacteraemia. J Med Microbiol 2013; 62(Pt 1): 155-6.
[6]
Todar K. Pathogenic clostridia Ken Todar’s Microbial World. University of Wisconsin-Madison 2005.
[7]
Reddy P, Bleck TP. Clostridium tetani (tetanus) Principles and Practice in Infectious Diseases. 7th Eds. Philadelphia: Churchill Livingstone 2010; pp. 3091-6.
[8]
Thwaites CL, Farrar JJ. Preventing and treating tetanus. BMJ 2003; 326(7381): 117-8.
[9]
Blencowe H, Lawn J, Vandelaer J, Roper M, Cousens S. Tetanus toxoid immunization to reduce mortality from neonatal tetanus. Int J Epidemiol 2010; 39(Suppl. 1): i102-9.
[10]
Schiavo G, Benfenati F, Poulain B, et al. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 1992; 359(6398): 832-5.
[11]
Brüggemann H, Bäumer S, Fricke WF, et al. The genome sequence of Clostridium tetani, the causative agent of tetanus disease. Proc Natl Acad Sci USA 2003; 100(3): 1316-21.
[12]
Hassel B. Tetanus: Pathophysiology, treatment, and the possibility of using botulinum toxin against tetanus-induced rigidity and spasms. Toxins (Basel) 2013; 5(1): 73-83.
[13]
Neema M, Karunasagar I, Karunasagar I. In silico identification and characterization of novel drug targets and outer membrane proteins in the fish pathogen Edwardsiella tarda. Open Access Bioinformatics 2011; 3: 37-42.
[14]
Sakharkar KR, Sakharkar MK, Chow VT. A novel genomics approach for the identification of drug targets in pathogens, with special reference to Pseudomonas aeruginosa. In Silico Biol 2008; 4(3): 320-8.
[15]
Dutta A, Singh SK, Ghosh P, Mukherjee R, Mitter S, Bandyopadhyay D. In silico identification of potential therapeutic targets in the human pathogen Helicobacter pylori. In Silico Biol 2002; 6(1, 2): 45-50.
[16]
Rathi B, Sarangi AN, Trivedi N. Genome subtraction for novel target definition in Salmonella typhi. Bioinformation 2009; 4(4): 143-50.
[17]
Sarangi AN, Aggarwal R, Rahman Q, Trivedi N. Subtractive genomics approach for in silico identification and characterization of novel drug targets in Neisseria Meningitides Serogroup B. J Comput Sci Syst Biol 2009; 2(5): 255-8.
[18]
Amineni U, Pradhan D, Marisetty H. In silico identification of common putative drug targets in Leptospira interrogans. J Chem Biol 2010; 3(4): 165-73.
[19]
Wu CH, Apweiler R, Bairoch A, et al. The Universal Protein Resource (UniProt): an expanding universe of protein information. Nucleic Acids Res 2006; 34(Suppl. 1): D187-91.
[20]
Huang Y, Niu B, Gao Y, Fu L, Li W. CD-HIT Suite: A web server for clustering and comparing biological sequences. Bioinformatics 2010; 26(5): 680-2.
[21]
Zhang R, Ou HY, Zhang CT. DEG: a database of essential genes. Nucleic Acids Res 2004; 32(Suppl. 1): D271-2.
[22]
Moriya Y, Itoh M, Okuda S, Yoshizawa AC, Kanehisa M. KAAS: an automatic genome annotation and pathway reconstruction server. Nucleic Acids Res 2007; 35(Suppl. 2).W182-5
[23]
Gardy JL, Laird MR, Chen F, et al. PSORTb v.2.0: expanded prediction of bacterial protein subcellular localization and insights gained from comparative proteome analysis. Bioinformatics 2005; 21(5): 617-23.
[24]
Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL workspace: A web-based environment for protein structure homology modelling. Bioinformatics 2006; 22(2): 195-201.
[25]
Bagos PG, Liakopoulos TD, Spyropoulos IC, Hamodrakas SJ. PRED-TMBB: A web server for predicting the topology of β-barrel outer membrane proteins. Nucleic Acids Res 2004; 32(Suppl. 2).W400-4
[26]
Laskowski RA, Watson JD, Thornton JM. ProFunc: A server for predicting protein function from 3D structure. Nucleic Acids Res 2005; 33(Suppl. 2).W89-93
[27]
Attwood TK, Kell DB, McDermott P, Marsh J, Pettifer SR, Thorne D. Utopia documents: Linking scholarly literature with research data. Bioinformatics 2010; 26(18): i568-74.
[28]
Bakheet TM, Doig AJ. Properties and identification of human protein drug targets. Bioinformatics 2009; 25(4): 451-7.
[29]
Sakharkar KR, Sakharkar MK, Chow VT. A novel genomics approach for the identification of drug targets in pathogens, with special reference to Pseudomonas aeruginosa. In Silico Biol 2004; 4(3): 355-60.
[30]
Dutta A, Singh SK, Ghosh P, Mukherjee R, Mitter S, Bandyopadhyay D. In silico identification of potential therapeutic targets in the human pathogen Helicobacter pylori. In Silico Biol 2006; 6: 43-7.
[31]
Chong CE, Lim BS, Nathan S, Mohamed R. In silico analysis of Burkholderia pseudomallei genome sequence for potential drug targets. In Silico Biol 2006; 6(4): 341-6.
[32]
Munikumar M, Priyadarshini IV, Pradhan D, Sandeep S, Umamaheswari A, Vengamma B. In silico identification of common putative drug targets among the pathogens of bacterial meningitis. Biochem Anal Biochem 2012; 1(8): 123.
[33]
Johnson JE, Cornell RB. Amphitropic proteins: Regulation by reversible membrane interactions (review). Mol Membr Biol 1999; 16(3): 217-35.
[34]
Alenghat FJ, Golan DE. Membrane protein dynamics and functional implications in mammalian cells. Curr Top Membr 2013; 72: 89-120.
[35]
Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov 2006; 5(12): 993-6.
[36]
Koebnik R, Locher KP, Van Gelder P. Structure and function of bacterial outer membrane proteins: Barrels in a nutshell. Mol Microbiol 2000; 37(2): 239-53.
[37]
Bakheet TM, Doig AJ. Properties and identification of antibiotic drug targets. BMC Bioinformatics 2010; 11(1): 195.
[38]
Hurdle JG, O’Neill AJ, Chopra I, Lee RE. Targeting bacterial membrane function: An underexploited mechanism for treating persistent infections. Nat Rev Microbiol 2011; 9(1): 62-75.


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Article Details

VOLUME: 14
ISSUE: 6
Year: 2019
Page: [532 - 540]
Pages: 9
DOI: 10.2174/1574893613666181114095736
Price: $58

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