Drug Target Identification and Prioritization for Treatment of Ovine Foot Rot: AnIn SilicoApproach

Abstract

Ovine foot rot is an infection of the feet of sheep, mainly caused byDichelobacter nodosus. In its virulent form, it is highly contagious and debilitating, causing significant losses in the form of decline in wool growth and quality and poor fertility. Current methods of treatment are ineffective in complete eradication. Effective antibiotic treatment of foot rot is hence necessary to ensure better outcomes during control phases by reduction in culling count and the possibility of carriers of the infection. Using computational approaches, we have identified a set of 297 proteins that are essential to theD. nodosusand nonhomologous with sheep proteins. These proteins may be considered as potential vaccine candidates or drug targets for designing antibiotics against the bacterium. This core set of drug targets have been analyzed for pathway annotation to identify 67 proteins involved in unique bacterial pathways. Choke-point analysis on the drug targets identified 138 choke-point proteins, 29 involved in unique bacterial pathways. Subcellular localization was also predicted for each target to identify the ones that are membrane associated or secreted extracellularly. In addition, a total of 13 targets were identified that are common in at least 10 pathogenic bacterial species.