The Identification of Common Druggable Targets For Acute Dysentery in Four Pathogenic Bacteria, Shigella, Salmonella, Campylobacter and E.Coli

Abstract

Purpose: Dysentery is a severe form of diarrhea and caused by four bacteria include Shigella, Campylobacter, E.coli and Salmonella. They are responsible for higher morbidity and mortality rates resulting from dysentery every year across the world. Antibiotic therapy of this disease plays a critical role in decreasing the prevalence as well as the fatality rate of this infection. However, the management of this disease remains challenging, owing to the overall increase in resistance against many antimicrobials. Hence, it has become important to identify as well as develop therapeutic methods presenting novel avenues for infections. In the current study, proteome based mapping was utilized to find the potential drug targets for dysentery. There is need to identify novel drug and vaccine targets to control this disease. This study is designed to identify new drug targets to develop drug and vaccines to battle bacillary dysentery. Subtractive genomics approach was used in this study to find novel drug targets.
 Methodology: The proteomes of Shigella, E. coli, Campylobacter and Salmonella were retrieved from Uniprot. Paralogs in these proteomes were removed by CD-HIT. Gene essentiality was screened by Geptop server 2.0. Host-pathogen interaction was analyzed through HPIDB database. To identify non-homologous proteins, the essential proteins were analyzed in Blastp against Homo sapiens (H. sapiens). The unique metabolic pathways were recognized by comparison of metabolic pathways of selected strains of bacteria and H. sapiens using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Subcellular localization and functional classification of proteins involved in unique metabolic pathways were analyzed through PSORTb and SVMProt. Druggability potential of unique essential proteins was investigated using the DrugBank database.
 Findings: Over all analysis showed 7 proteins that were common in all four bacteria. These proteins were essential to pathogens. Out of 7 proteins 6 proteins MURA, MURG, DAPA, MURB, DAPE, DnaA are reported as a drug target in different bacteria and one protein DAPD is novel. The study will enable the development of natural and cost-effective drugs against dysentery infections.
 Recommendation: However, further validations are necessary to confirm their drug effectiveness and biocompatibility.