Campylobacter jejuni (CJJ) is a source of bacterial foodborne diarrhea globally. Mostly found prevalent in children in the developing countries that may lead to mortality. The upsurge in antimicrobial resistance is causing hindrance in the treatment, as highlighted by CDC and WHO. The study hypothesized the application of subtractive genomics approach coupled with metabolic pathway to reveal unidentified essential proteins that could serve as potential drug target (s). The approach was employed to model the druggable proteome of C. jejuni resistant strain 81-176. We obtained 728/1744 non-homologous essential proteins by performing sequence similarity search against host proteome and DEG server, respectively. The KAAS annotated metabolic pathway information; PSORTb predicted their sub cellular localization and SVMPro functional annotated 104 hypothetical proteins while the Drug Bank for the druggability analysis. We found 04/104 protein druggable viz. synaptic vesicular amine transporter, Uracil-DNA glycosylase, Laccase domain protein YfiH, and Phosphoenolpyruvate protein phosphor transferase. The study has revealed a formerly uncharacterized pool of C. jejuni proteins that can play a significant role in controlling CJJ infection and presented previously uncharacterized four proteins as potential drug targets. These potential drug targets can further be explored employing structure-based and other biochemical methods by the scientific community.

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