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Online Journal of Bioinformatics ©
Volume 12(1):149-169, 2011
Identification of potential drug targets in M1 strain of Streptococcus pyogenes by differential genomics
Nidhi Trivedi, Aditya Narayan Sarangi, Sita Naik, Rakesh Aggarwal.
1Biomedical Informatics Centre, School of Telemedicine and Biomedical Informatics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
Trivedi N, Sarangi AN, Naik S, Aggarwal R., Identification of potential drug targets in M1 strain of Streptococcus pyogenes by differential genomics, Online J Bioinformatics,† 12(1):149-169, 2011. Availability of complete genome sequences of pathogenic organisms and their protein complements has made it possible to determine potential drug targets and vaccine candidates against these pathogens using computer-based data analysis techniques. Differential genomics is one such approach. It involves identification of bacterial proteins that are non-homologous to human proteins, and at the same time, indispensable for the pathogenís survival. We used this in silico approach for identification of essential proteins in Streptococcus pyogenes strain M1, a Gram-positive bacterium, which is an important human pathogen. Of the 1693 proteins in this bacteriumís proteome, 1193 protein sequences were found to have no homologous human proteins. Of these, 269 proteins were identified as essential for the bacterium. Analysis using CELLO, that allows prediction of subcellular localization of proteins, showed that 51 of these essential S. pyogenes strain M1 proteins were membrane proteins and thus more amenable as drug targets. Further, using the KEGG Automatic Annotation Server, we identified six unique metabolic pathways that exist in this bacterium but not in human and 17 essential S. pyogenes proteins that are involved in these bacterial pathways. The essential proteins that have not been previously characterized were studied using the SVM-Prot server; this showed that 14 uncharacterized but essential bacterial proteins were putative transmembrane proteins. In conclusion, we have identified essential proteins of S. pyogenes strain M1 for future study as drug targets; of these, 51 proteins with membrane localization, 17 proteins that act in metabolic pathways unique to this bacterium and 14 uncharacterized proteins with putative transmembrane localization should be of particular interest.
Keywords: Streptococcus pyogenes, differential genomics approach, essential proteins, therapeutic targets