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OJBTM
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
ABSTRACT
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 pathogen’s 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 bacterium’s 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
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