Comparative genomic analysis of Rickettsia rickettsii for identification of drug and vaccine targets: tolC as a proposed candidate for case study

Acta Tropica
Pramod Kumar MauryaAshutosh Mani

Abstract

Antibiotic resistance is increasing rapidly in pathogenic organisms, creating more complications for treatment of diseases. Rocky Mountain spotted fever (RMSF) is a neglected tropical disease in humans caused by Rickettsia rickettsii for which no effective therapeutic is available. Subtractive genomics methods facilitate the characterization of non-homologous essential proteins that could be targeted for the discovery of potential therapeutic compounds against R. rickettsii to combat RMSF. Present study followed an in-silico based methodology, involving scanning and filtering the complete proteome of Rickettsia rickettsii by using several prioritization parameters in the search of potential candidates for drug development. Further the putative targets were subjected to series of molecular dockings with ligands obtained from PDB ligand database to identify suitable potential inhibitors. The comparative genomic analysis revealed 606 non-homologous proteins and 233 essential non-homologous proteins of R. rickettsii. The metabolic pathway analysis predicted 120 proteins as putative drug targets, out of which 56 proteins were found to be associated with metabolic pathways unique to the bacteria and further subcellular localization a...Continue Reading

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