IDENTIFICATION OF PUTATIVE DRUG TARGETS IN MASTITIS CAUSING STAPHYLOCOCCUS AUREUS BY IN SILICO APPROACH
Keywords:Mastitis, Insilico, S aureus, DEG
Objective: In the present study an attempt has been made by the use of a computational approach to investigate putative drug targets in Staphylococcus aureus.
Methods: In silico comparative analysis of the metabolic pathways between the pathogen and the Bos taurus was carried out. Further detection of bacterial genes that are non homologous to host, but are essential for the survival of the pathogen represents a promising means of identifying novel drug targets. Metabolic pathways were obtained from the metabolic pathway database Kyoto Encyclopedia of Genes and Genomes (KEGG) and were compared to identify unique pathways present only in the pathogen and absent in the host.
Results: We have identified total 1930 proteins, which are non homologous to Bos taurus protein sequences and among them 374 enzymes are found to be essential for survival of the S. aureus according to the database of essential genes (DEG) database. Further, 10 proteins were predicted as cytoplasmic and cell wall associated proteins, which could serve as potential drug target candidates.
Conclusion: The identified potential drug targets form a platform for further investigation in discovery of novel therapeutic agents against S. aureus.
Allore HG. A review of the incidence of mastitis in buffaloes and cattle. Pak Vet J 1993;13:1-7.
De-Oliveira SS, Povoa DC, Nascimento JS, Pereira MS, Siqueira JP, Bastos MC. Antimicrobial substances produced by Staphylococcus aureus strains isolated from cattle in Brazil. Lett Appl Microbiol 1998;27:229-34.
Bhatt VD, Patel MS, Joshi CG, Kunjadia A. Identification and antibiogram of microbes associated with bovine mastitis. Anim Biotechnol 2011;22:163-9.
Kuhlmann J. Drug research from the idea to the product. Int J Clin Pharmacol Ther 1997;35:541-52.
Amineni U, Pradhan D, Marisetty H. In silico identification of common putative drug targets in Leptospira interrogans. J Chem Biol 2010;3:165-73.
Munikumar M, Vani Priyadarshini I, Pradhan D, Sandeep S, Umamaheswari A. In silico identification of common putative drug targets among the pathogens of bacterial meningitis. Biochem Anal Biochem 2012;1:1-7.
Koteswara RG, Nagamalleswara RK, Krishna B, Aravind S. In silico identification of potential therapeutic targets in Clostridium botulinum by the approach subtractive genomics. Int J Bioinf Res 2010;2. doi: 10.9735/0975-3087.2.2.12-16. [Article in Press]
Huang Y, Niu B, Gao Y, Fu L, Li W. CD-HIT Suite: a web server for clustering and comparing biological sequences. Bioinformatics 2010;26:680-2.
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;2:255-8.
Zhang R, Ou HY, Zhang CT. DEG: a database of essential genes. Nuc Acids Res 2004;32(Suppl 1):D271-D272.
Moriya Y, Itoh M, Okuda S, Yoshizawa AC, Kanehisa M. KAAS: an automatic genome annotation and pathway reconstruction server. Nuc Acids Res 2007;35:W182â€“W185.
Gardy JL, Laird MR, Chen F, Rey S, Walsh C, Ester M, et al. PSORTb v. 2.0:expanded prediction of bacterial protein subcellular localization and insights gained from comparative proteome analysis. Bioinformatics 2005;21:617-23.
Kurjogi MM, Kaliwal BB. In silico identification and characterization of potential drug targets in bovine Herpes Virus 4, causing bovine mastitis. Adv Biol 2014. doi.org/10.1155/2014/369213. [Article in Press]
Kumar GS, Sarita S, Kumar GM, Pant K, Seth P. Definition of potential targets in Mycoplasma pneumoniae through subtractive genome analysis. J Antivirals Antiretrovirals 2010;2.38.
Butt AM, Nasrullah I, Tahir S, Tong Y. Comparative genomics analysis of Mycobacterium ulcerans for the identification of putative essential genes and therapeutic candidates. PloS One 2012;7:e43080. doi: 10.1371/journal.pone.0043080. [Article in Press]
Volker C, Brown JR. Bioinformatics and the discovery of novel anti-microbial targets. Curr Drug Targets Infect Disord 2002;2:279-90.
Judson N, Mekalanos JJ. Tn Ara Out, a transposon-based approach to identify and characterize essential bacterial genes. Nat Biotechnol 2000;18:740-5.
Georrge JJ, Umrania V. In silico identification of putative drug targets in Klebsiella pneumonia MGH 78578. Indian J Biotechnol 2011;10:432-9.
Angamuthua K, Piramanayagama S. In silico identification of putative drug targets in Mycoplasma hominis using differential metabolic pathway analysis. Int J Pharm Bio Sci 2012;3:391-8.
Forsyth R, Haselbeck RJ, Ohlsen KL, Yamamoto RT, Xu H, Trawick JD, et al. A genomeâ€wide strategy for the identification of essential genes in Staphylococcus aureus. Mol Microbiol 2002;43:1387-400.
Chaudhuri RR, Allen AG, Owen PJ, Shalom G, Stone K, Harrison M, et al. Comprehensive identification of essential Staphylococcus aureus genes using Transposon-Mediated Differential Hybridisation (TMDH). BMC Genomics 2009;10:291.
Gardy JL, Brinkman FS. Methods for predicting bacterial protein subcellular localization. Nat Rev Microbiol 2006;4:741-51.
Anishetty S, Pulimi M, Pennathur G. Potential drug targets in Mycobacterium tuberculosis through metabolic pathway analysis. Comput Biol Chem 2005;29:368-78.
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;4:355-60.