In silico prediction of drug targets in Vibrio cholerae
- 355 Downloads
Identification of potential drug targets is the first step in the process of modern drug discovery, subjected to their validation and drug development. Whole genome sequences of a number of organisms allow prediction of potential drug targets using sequence comparison approaches. Here, we present a subtractive approach exploiting the knowledge of global gene expression along with sequence comparisons to predict the potential drug targets more efficiently. Based on the knowledge of 155 known virulence and their coexpressed genes mined from microarray database in the public domain, 357 coexpressed probable virulence genes for Vibrio cholerae were predicted. Based on screening of Database of Essential Genes using blastn, a total of 102 genes out of these 357 were enlisted as vitally essential genes, and hence good putative drug targets. As the effective drug target is a protein which is only present in the pathogen, similarity search of these 102 essential genes against human genome sequence led to subtraction of 66 genes, thus leaving behind a subset of 36 genes whose products have been called as potential drug targets. The gene ontology analysis using Blast2GO of these 36 genes revealed their roles in important metabolic pathways of V. cholerae or on the surface of the pathogen. Thus, we propose that the products of these genes be evaluated as target sites of drugs against V. cholerae in future investigations.
KeywordsVibrio cholerae Virulence genes Essential genes Drug targets Coexpressed genes
The authors acknowledge the DBT center for bioinformatics facility at Department of Bioscience and Biotechnology, Banasthali University, Banasthali, India for providing essential facilities for completion of this research work. The authors also wish to thank Mr. Manish Roorkiwal, Guru Gobind Singh Indraprastha University, Delhi for critically reviewing the manuscript.
No competing financial interests exist.
- Perumal D, Lim CS, Sakharkar KR, Sakharkar MK (2007) Differential genome analyses of metabolic enzymes in Pseudomonas aeruginosa for drug target identification. In Silico Biol 7:0032Google Scholar
- Roemer T, Jiang B, Davison J, Ketela T, Veillette K, Breton A, Tandia F, Linteau A, Sillaots S, Marta C, Martel N, Veronneau S, Lemieux S, Kauffman S, Becker J, Srorms R, Boone C, Bussey H (2003) Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Mol Microbiol 50:167–181PubMedCrossRefGoogle Scholar
- Sakharkar KR, Sakharkar MK, Chow VTK (2004) A novel genomics approach for the identification of drug targets in pathogens, with special reference to Pseudomonas aeruginosa. In Silico Biol 4:0028Google Scholar
- Sharma V, Gupta P, Dixit A (2008) In silico identification of putative drug targets from different metabolic pathways of Aeromonas hydrophila. In Silico Biol 8:0026Google Scholar
- Sridhar P, Song B, Kahveci T, Ranka S (2007) Mining metabolic networks for optimal drug targets. Pac Symp Biocomput 13:291–302Google Scholar