Subtractive Genomics Approach for in Silico Identification of Novel Drug Targets and Epitopes for Vaccine Design in Treponema Pallidum Subsp. Pallidum Str. Nichols

In silico differential genomics helps to identify genes that encode for unique metabolism with relation to human. The genomic database provides a vast amount of useful information for the drug target identification. The subtractive dataset obtained comparatively between the human and the pathogen genome, differentially provides information about the genes that are likely to be essential to the pathogen but is not part of the host (human).This approach has given fruitful results in recent times to identify essential genes in Pseudomonas aeruginosa. The same strategy is used to analyse the whole genome sequence of the Treponema pallidum subsp. pallidum str. Nichols. Three putative membrane-bound drug targets have been derived step-wise, out of the 301 essential genes that have been predicted. The putative drug targets include the drug targets taking part in unique metabolic pathways that are situated in the membrane and are specific to the pathogen. Structure prediction of the membrane bound drug targets is done along with B-cell epitope mapping that highlights the immunogenic part of a protein. Syphilis is characterised by many asymptomatic and latent clinical stages. In spite of effective prophylaxis by use of penicillin, there has been increase in the resistance in the pathogen and an alternative is required due to penicillin allergic pregnant women. In silico study for identification of potential drug targets has been possible due availability of whole proteomic data of Treponema pallidum subsp. Pallidum str. Nichols. INTRODUCTION: Treponema pallidum subsp. pallidum str. Nichols is one of the strains that cause venereal disease syphilis. This was isolated originally from neurosyphilitic patient. Others strains like pallidum str pertenue, carateum and endemicum cause the skin infections yaws, pinta and bejel, respectively. Treponema pallidum subsp. pallidum str. Nichols is slender helical shaped gram negative bacteria that have an unusual cell envelope when compared to other gram negative bacteria. Pathogenicity of the bacteria is mainly due to the presence of the capsule. It consists of the outer and inner membrane that helps in studying the membrane associated proteins . This organism is the causative agent of venereal syphilis at the molecular level. The sexual transmitted disease was first discovered in Europe at the end of the fifteenth century, however, the causative agent was not identified until 1905 . Syphilis was reported to be the third most commonly reported transmittable disease in USA.