Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Department of Biotechnology, Mirpur University of Science and Technology (MUST).
Pak J Pharm Sci. 2021 Jul;34(4):1359-1367.
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.
空肠弯曲菌（CJJ）是全球细菌性食源性腹泻的源头。主要在发展中国家的儿童中普遍存在，可能导致死亡。正如疾病预防控制中心和世界卫生组织所强调的那样，抗微生物药物耐药性的激增正在阻碍治疗。该研究假设应用消减基因组学方法结合代谢途径来揭示未被识别的必需蛋白质，这些蛋白质可能作为潜在的药物靶标（s）。该方法被用于对 C. jejuni 耐药菌株 81-176 进行可成药性蛋白质组模型研究。我们通过对宿主蛋白质组和 DEG 服务器分别进行序列相似性搜索，获得了 728/1744 个非同源必需蛋白质。KAAS 注释的代谢途径信息；PSORTb 预测了它们的亚细胞定位，SVMPro 功能注释了 104 个假设蛋白质，而 Drug Bank 则进行了可成药性分析。我们发现 04/104 个蛋白质是可成药的，即突触囊泡胺转运蛋白、尿嘧啶-DNA 糖基化酶、Laccase 结构域蛋白 YfiH 和磷酸烯醇丙酮酸蛋白磷酸转移酶。该研究揭示了空肠弯曲菌中以前未被描述的蛋白质池，这些蛋白质可能在控制空肠弯曲菌感染中发挥重要作用，并提出了以前未被描述的四个蛋白质作为潜在的药物靶标。这些潜在的药物靶标可以进一步由科学界通过基于结构的和其他生化方法进行探索。
