COMPUTATIONAL IDENTIFICATION OF PUTATIVE DRUG TARGETS IN MALASSEZIA GLOBOSA BY SUBTRACTIVE GENOMICS AND PROTEIN CLUSTER NETWORK APPROACH
DOI:
https://doi.org/10.22159/ijpps.2017v9i9.20609Keywords:
Malassezia globosa, Homo sapiens, Comparative genomics, Protein-protein interactions, Drug targetsAbstract
Objective: Yeast commonly causes superficial mycoses similar to the dermatophytes. Superficial mycoses were reported with an estimated incidence of ∼140,000,000 cases/year worldwide and most frequently caused by Malassezia globosa and Malassezia furfur. Treatment available for these conditions is limited and with side effects. Moreover, termination of the treatment may result in the reoccurrence of the disease. The objective of this research was to identify the putative drug targets using computational approaches.
Methods: The analysis of genome sequence improves the understanding of diseases which leads to better treatment. Comparison of the genome of the pathogen with the host at the molecular level is suitable for performing the sequence based prediction of protein-protein interaction network, which also forms the basis of drug target identification leading to the discovery of new drugs for the improved treatment.
Results: Out of 100 pathways of M. globosa, 95 were common to the host and 5 were unique to the pathogen. Total common and unique targets from common pathways are 1704 and 300, respectively. A unique target from unique pathways and 147 from common pathways were non-homologous targets. From this, 46 targets were screened out as essential and processed in the next phase to identify the clustered targets which resulted with three clusters based on their biological role and subcellular location.
Conclusion: In this study, putative drug targets were identified in M. globosa using in silico approaches of subtractive genomics and cluster network which will help in the next level of drug discovery such as lead identification for the novel targets.
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Fleming RV, Walsh TJ, Anaissie EJ. Emerging and less common fungal pathogens. Infectious Diseases Clin North Am 2002;16:915-33.
Garbino J, Kolarova L, Lew D, Hirschel B, Rohner P. Fungemia in HIV-infected patients: a 12 y study in a tertiary care hospital. AIDS Patient Care STDs 2001;15:407-10.
Havlickova B, Czaika VA, Friedrich M. Epidemiological trends in skin mycoses worldwide. Mycoses 2008;51:2-15.
Batra R, Boekhout T, Gueho E, Cabanes FJ, Dawson TL, Gupta AK. Malassezia Baillon, emerging clinical yeasts. FEMS Yeast Res 2005;5:1101-3.
Moniri R, Nazeri M, Amiri S, Asghari B. Isolation and identification of Malassezia spp. in pytiriasis versicolor in Kashan, Iran. Pak J Med Sci 2009;25:837-40.
Byung HO, Yang EL, Yong BC, Kyu JA. Epidemiologic study of Malassezia yeasts in seborrheic dermatitis patients by the analysis of 26S rDNA PCR-RFLP. Ann Dermatol 2010; 22:149-55.
Sampurna BP, Atreyi C, Anita N, Maitrayee B, Rina G, Bandopadhyay M, et al. A study of the prevalence of different species of Malassezia causing pityriasis versicolor and sites of distribution of lesion in a tertiary care hospital in Kolkatta, India. Int J Curr Microbiol Appl Sci 2015;4:471-8.
Hort W, Mayser P. Malassezia virulence determinants. Curr Opin Infect Dis 2011;24:100-5.
Gueho E, Boekhout T, Ashbee HR, Guillot J, Van Belkurn A, Faergemann J. The role of Malassezia species in the ecology of human skin and as pathogens. Med Mycol 1998;36:220-9.
Crespo Erchiga V, Ojeda Martos A, Vera Casano A, Crespo Erchiga A, Sanchez Fajardo F. Malassezia globosa as the causative agent of pityriasis versicolor. Br J Dermatol 2000;143:799-803.
Thomas L, Dawson JR. Malassezia globosa and restricta: Breakthrough understanding of the etiology and treatment of dandruff and seborrheic dermatitis through whole genome analysis. J Invest Dermatol 2007;12:15-9.
Baran R, Maibach HI. editors. Schwartz JR, Cardin CW, Dawson TL. Dandruff and seborrheic dermatitis. Textbook of Cosmetic Dermatology London: UK; 2004. p. 259-72.
Crespo Erchiga V, Delgado Florencio V. Malassezia species in skin diseases. Curr Opin in Infect Dis 2002;15:133-42.
Roberts L, Simpson S. Drug Resistance. Deadly defiance. Introduction to special Issue. Science 2008;321:55.
Christophe LM, Verlinde CL, Hannaert V, Blonski C, Willson M, Perie JJ, et al. Glycolysis as a target for the design of new anti-trypanosome drugs. Drug Resist Updates 2001;4:50-65.
Oviya IR, Sharanya M, Jeyam M. Phytocompounds from Sphaeranthus indicus and Wrightia tinctoria targeting fungal aspartate pathway-an in silico evaluation. Adv Biomed Pharm 2015;2:13-21.
Sarkar M, Maganti L, Ghoshal N, Dutta C. In silico quest for putative drug targets in Helicobacter pylori HPAG1:molecular modeling of candidate enzymes from lipopolysaccharide biosynthesis pathway. J Mol Model 2012;18:1855-66.
Collins JF, Coulson AF, Lyall A. The significance of protein sequence similarities. CABIOS Comput Appl Biosci 1988;4:67-71.
Pearson WR. Comparison of methods for searching protein sequence databases. Protein Sci 1995;4:1145-60.
Pearson WR. Effective protein sequence comparison. Methods Enzymol 1996;266:227-58.
Luo H, Lin Y, Gao F, Zhang CT, Zhang R. DEG 10, an update of the database of essential genes that includes both protein coding genes and noncoding genomic elements. Nucleic Acids Res 2014;42:574-80.
Jadhav A, Ezhilarasan V, Prakash Sharma O, Pan A. Clostridium-DT(DB): a comprehensive database for potential drug targets of Clostridium difficile. Comput Biol Med 2013;43:362-7.
Aditya NS, Rakesh A, Qamar R, Nidhi T. Subtractive genomics approach for in silico identification and characterisation of novel drug targets in Neisseria Meningitis serogroup B. J Comput Sci Syst Biol 2009;2:255-8.
Zhang R, Lin Y. DEG 5.0, a database of essential genes in both prokaryotes and eukaryotes. Nucleic Acids Res 2009;37:455-8.
Raman K, Yeturu K, Chandra N. target TB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis. BMC Syst Biol 2008;2:1-21.
Kushwaha SK, Shakya M. Protein interaction network analysis-approach for potential drug target identification in Mycobacterium tuberculosis. J Theor Biol 2010;262;284-94.
Cui T, Zhang L, Wang X, He ZG. Uncovering new signaling proteins and potential drug targets through the interactome analysis of Mycobacterium tuberculosis. BMC Genomics 2009;10:1-10.
Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T. Cytoscape 2.8:new features for data integration and network visualization. Bioinformatics 2011;27:431-2.
Vipin G, Shazia H, Sood U, Jack AG, Meenakshi R, Ken F, et al. Comparative genomic analysis of novel Acinetobacter symbionts: a combined system biology and genomics approach. Nat: Sci Reports 2016;6:1-12.
Bhasin M, Raghava GPS. ESLpred: SVM based method for subcellular localization of eukaryotic proteins using dipeptide composition and PSI-BLAST. Nucleic Acids Res 2004;32:414-9.
Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, et al. DrugBank 3.0:a comprehensive resource for ‘omics’ research on drugs. Nucleic Acids Res 2011;39:1035-41.
Chen X, Ji ZL, Chen YZ. TTD: Therapeutic target database. Nucleic Acids Res 2002;30:412-5.
Barh D, Sandeep T, Neha J, Amjad A, Anderson, Amarendra NM, et al. In silico subtractive genomics for target identification in human bacterial pathogens. Drug Dev Res 2011;72:162-77.
Madagi S, Patil VM, Sadegh S, Singh AK, Garwal B, Banerjee A, et al. Identification of membrane associated drug targets in Borrelia burgdorferi ZS7-subtractive genomics approach. Bioinformation 2011;6:356-9.
Butt AM, Tahir S, Nasrullah I, Idrees M, Lu J, Tong Y. Mycoplasma genitalium: a comparative genomics study of metabolic pathways for the identification of drug and vaccine targets. J Mol Epidemiol Evolutionary Genetics Infectious Diseases 2012;12:53-62.
Arvind A, Jain V, Saravanan P, Mohan CG. Uridine monophosphate kinase as a potential target for tuberculosis: from target to lead identification. Interdiscip Sci: Comput Life Sci 2013;5:296-311.
Hosen MI, Tanmoy AM, Mahbuba DA, Salma U, Nazim M, Islam MT, et al. Application of a subtractive genomics approach for Insilico identification and characterization of novel drug targets in Mycobacterium tuberculosis F11. Interdiscip Sci: Comput Life Sci 2014;6:48-56.
Singh S, Bukhsh Singh D, Singh A, Gautam B, Tam G, Dwidevi S, et al. An approach for identiï¬cation of novel drug targets in Streptococcus pyogenes SF370 through pathway analysis. Interdiscip Sci: Comput Life Sci 2016;3:388-94.
Damte D, Suh J, Lee S, Yohannes SB, Akil Hossain, Park S. Putative drug and vaccine target protein identification using comparative genomic analysis of KEGG annotated metabolic pathways of Mycoplasma hyopneumoniae. Genomics 2013;102:47-56.
Munikumar M, Vani Priyadarshini I, Pradhan D, Sandeep S, Umamaheswari A, Bhuma Vengamma. In silico identification of common putative drug targets among the pathogens of bacterial meningitis. Biochem Anal Biochem 2012;1:1-7.
Li X, Hou Y, Yue L, Liu S, Du J, Sun S. Potential targets for antifungal drug discovery based on growth and virulence in Candida albicans. Antimicrob Agents Chemother 2015;59:5885-91.
Kobayashi K, Ehrlich SD, Albertini A, Amati G, Andersen KK, Arnaud M, et al. Essential Bacillus subtilis genes. Proc Natl Acad Sci 2003;100:4678-83.
Galperin MY, Koonin EV. Conserved hypothetical proteins: prioritization of targets for experimental study. Nucleic Acids Res 2004;32:5452-63.
Goutam M, Arunima G, Sourav S, Paramita S, Naboneeta S. In silico identification of potential therapeutic targets in the human pathogen Neisseria Meningitidis MC58. Int J Pharm Eng 2012;1:1-4.
Abadio AKR, Kioshima ES, Teixeria MM, Martins NF, Maigret B, Felipe MS. Comparative genomics allowed the identification of drug targets against human fungal pathogens. BMC Genomics 2011;12:1-10.
Kaltdorf M, Srivastava M, Gupta SK, Liang C, Binder J, Dietl AM, et al. Systematic identification of antifungal drug targets by a metabolic network approach. Front Mol Biosci 2016;3:1-19.
Jeong H, Mason SP, Barbasi AL, Oltavi ZN. Lethality and centrality in protein networks. Nature 2001;411:41-2.
Raman K, Yeturu K, Chandra N. target TB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis. BMC Syst Biol 2008;2:1-21.
Ho Y, Gruhler A, Heilbut A, Bader GD, Moore L, Adams SL. Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 2002;415:180-3.
Pavan G, Manjunatha H, Sharath P. Cluster analysis of protein-protein interaction network of Mycobacterium tuberculosis during host infection. Adv Biores 2015;6:38-46.
Klipp E, Wade RC, Kummer U. Biochemical network-based drug-target prediction. Curr Opin Biotechnol 2010;21:511-6.
Pujol A, Mosca R, Farres J, Aloy P. Unveiling the role of network and systems biology in drug discovery. Trends Pharmacol Sci 2010;31:115-23.
Kumar HSS, Kumar V, Pattar S, Telkar S. Towards the construction of an interactome for a human WD40 protein family. Bioinformation 2016;12:54-61.
Morya VK, Kumari S, Kim E. Imperative pathway analysis to identify the potential drug target for Aspergillus infection. Int J Latest Trends Computing 2011;2:178-82.
Calderone R, Li D, Traven A. System-level impact of mitochondria on fungal virulence: to metabolism and beyond. FEMS Yeast Res 2015;15:1-11.
Murima P, McKinney JD, Pethe K. Targeting bacterial central metabolism for drug development. Chem Biol 2014;21:1423-32.
Myler PJ, Fasel N. editors. Opperdoes FR, Michels PA. The metabolic repertoire of Leishmania and implications for drug discovery. U. K Caister: Academic Press; 2008. p. 123-58.
Hema K, Priyadarshini IV, Pradhan D, Munikumar M, Sandeep S. Identification of putative drug targets and vaccine candidates for pathogens causing atherosclerosis. Biochem Anal Biochem 2015;4:1-9.
Sharma OP, Kumar MS. Essential proteins and possible therapeutic targets of Wolbachia endosymbiont and development of FiloBase-a comprehensive drug target database for Lymphatic filariasis. Sci Rep 2016;6:1-11.
Parvege M, Rahman M, Hossain MS. Genome-wide analysis of Mycoplasma hominis for the identification of putative therapeutic targets. Drug Target Insights 2014;8:51-62.
Tolkatchev D, Shaykhutdinov R, Xu P, Plamondon J, Watson DC, Young NM, et al. Three-dimensional structure and ligand interactions of the low molecular weight protein tyrosine phosphatase from Campylobacter jejuni. Protein Sci 2006;15:2381-94.
Chordia N, Lakhawat K, Kumar A. Identification of drug target properties and its validation on Helicobacter pylori. Can J Biotech 2017;1:44-9.
Anishetty S, Pulimi M, Pennathur G. Potential drug targets in Mycobacterium tuberculosis through metabolic pathway analysis. Comput Biol Chem 2005;29:368-78.
Kori P, Madagi SB. Chikungunya drug target database: a comprehensive database of chikungunya drug targets. Asian J Pharm Clin Res 2016;9:134-7.
Bhaskar BV, Chandra Babu TM, Rajendra W. Homology modeling and development of dihydrodipicolinate reductase inhibitors of Klebsiella pneumonia: a computational approach. Int J Curr Pharm Res 2016;8:71-6.
Daisy P, Pon Nivedha R, Helen Bakiya. In silico drug designing approach for biotin protein ligase of Mycobacterium tuberculosis. Asian J Pharm Clin Res 2013;6:103-7.
Mahendran R, Jeyabasker S, Manoharan S, Francis A, Shah U. In silico metabolic pathway analysis and docking analysis of Treponema pallidium subs. Pallidium Nichols for potential drug targets. Asian J Pharm Clin Res 2017;10:261-4.