Novel Drug Targets for Food-Borne Pathogen Campylobacter jejuni: An Integrated Subtractive Genomics and Comparative Metabolic Pathway Study.

Abstract

Campylobacters are a major global health burden and a cause of food-borne diarrheal illness and economic loss worldwide. In developing countries, Campylobacter infections are frequent in children under age two and may be associated with mortality. In developed countries, they are a common cause of bacterial diarrhea in early adulthood. In the United States, antibiotic resistance against Campylobacter is notably increased from 13% in 1997 to nearly 25% in 2011. Novel drug targets are urgently needed but remain a daunting task to accomplish. We suggest that omics-guided drug discovery is timely and worth considering in this context. The present study employed an integrated subtractive genomics and comparative metabolic pathway analysis approach. We identified 16 unique pathways from Campylobacter when compared against H. sapiens with 326 non-redundant proteins; 115 of these were found to be essential in the Database of Essential Genes. Sixty-six proteins among these were non-homologous to the human proteome. Six membrane proteins, of which four are transporters, have been proposed as potential vaccine candidates. Screening of 66 essential non-homologous proteins against DrugBank resulted in identification of 34 proteins with drug-ability potential, many of which play critical roles in bacterial growth and survival. Out of these, eight proteins had approved drug targets available in DrugBank, the majority serving crucial roles in cell wall synthesis and energy metabolism and therefore having the potential to be utilized as drug targets. We conclude by underscoring that screening against these proteins with inhibitors may aid in future discovery of novel therapeutics against campylobacteriosis in ways that will be pathogen specific, and thus have minimal toxic effect on host. Omics-guided drug discovery and bioinformatics analyses offer the broad potential for veritable advances in global health relevant novel therapeutics.