Abstract
Large genomic sequencing projects of pathogens as well as human genome leads to immense genomic and proteomic data which would be very beneficial for the novel target identification in pathogens. Subtractive genomic approach is one of the most useful strategies helpful in identification of potential targets. The approach works by subtracting the genes or proteins homologous to both host and the pathogen and identify those set of gene or proteins which are essential for the pathogen and are exclusively present in the pathogen. Subtractive genomic approach is employed to identify novel target in salmonella typhi. The pathogen has 4718 proteins out of which 300 are found to be essential (" indispensable to support cellular life") in the pathogen with no human homolog. Metabolic pathway analyses of these 300 essential proteins revealed that 149 proteins are exclusively involved in several metabolic pathway of S. typhi. 8 metabolic pathways are found to be present exclusively in the pathogen comprising of 27 enzymes unique to the pathogen. Thus, these 27 proteins may serve as prospective drug targets. Sub-cellular localization prediction of the 300 essential proteins was done which reveals that 11 proteins lie on the outer membrane of the pathogen which could be probable vaccine candidates.
Highlights
The availability of large amount of genomic data generated by the microbial genomes and the human genome project has revolutionized the field of drug-discovery against threatening human pathogens [1]
Subtractive genomic strategy is developed by assuming that the novel targets identified in the pathogen should be essential for the pathogen that is it should be involved in the replication, survival and a important component of various metabolic pathways and mechanisms occurring in the pathogen while at the same time should be absent on the host that is human and should have no homolog in human, so that when a drug or a lead compound is designed considering the potential target it should only be against the mechanism and functionality of the pathogen not the host
The current studies make use of the subtractive genomics approach and Database of Essential Genes (DEG) to analyze the complete genome of Salmonella typhi to search for potential vaccine candidates which would possibly lie on the surface membrane of the pathogen and drug targets
Summary
The availability of large amount of genomic data generated by the microbial genomes and the human genome project has revolutionized the field of drug-discovery against threatening human pathogens [1]. Salmonella enterica serovar typhi is a human-specific gram-negative pathogen causing enteric typhoid fever, a severe infection of the reticuloendothelial system [4], [5], [6] It has two strains CT18 (multiple drug resistant) [7] and Ty with a complete proteome of 4718 proteins. Detection of non-human homologs in the Protein sub cellular localization prediction involves the computational essential proteins of S. typhi with subsequent screening of the prediction of where a protein resides in a cell. Out of the 14 enzymes involved in LPS biosyntheseis pathway, 13 enzymes are found to be essential for the variability of the bacteria and could be probable drug targets and it did not show homology with any human protein. The results are summarized in Table No 3 (Supplementary material)
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