Department of Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam, AP, India.
Curr Drug Targets. 2013 May 1;14(5):601-11. doi: 10.2174/1389450111314050009.
Helicobacter species colonizes the stomach and are associated with the development of gastritis disease. Drugs for treatment of Helicobacter infection relieve pain or gastritis symptoms but they are not targeted specifically to Helicobacter pylori. Therefore, there is dire need for discovery of new drug targets and drugs for the treatment of H. pylori. The main objective of this study is to screen the potential drug targets by in silico analysis for the potent strains of H. pylori which include HpB38, HpP12, HpG27, Hpshi470 and HpSJM180. Genome and metabolic pathways of pathogen H. pylori and the host Homosapien sapiens are compared and genes which were unique to H. pylori were filtered and catalogued. These unique genes were subjected to gene property analysis to identify the potentiality of the drug targets. Among the total number of genes analysed in different strains of H. pylori nearly 558, 569, 539, 569, 567 number of genes in HpB38, HpP12, HpG27, Hpshi470 and HpSJM180 found qualified as unique molecules and among them 17 qualified as potential drug targets. Membrane fusion protein of hefABC efflux system, 50 S ribosomal protein L33, Hydrogenase expression protein/formation of HypD, Cag pathogenecity island protein X, Apolipoprotein N acyl transferase, DNA methyalse, Histone like binding protein, Peptidoglycan-associated lipoprotein OprL were found to be critical drug targets to H. pylori. Three (hefABC efflux system, Hydrogenase expression protein/formation of HypD, Cag pathogenecity island protein X) of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lending credence to our unique approach.
幽门螺杆菌定植于胃部,并与胃炎疾病的发展有关。用于治疗幽门螺杆菌感染的药物可以缓解疼痛或胃炎症状,但它们并非专门针对幽门螺杆菌。因此,迫切需要发现新的药物靶点和治疗幽门螺杆菌的药物。本研究的主要目的是通过计算机分析筛选出针对强毒力幽门螺杆菌菌株(包括 HpB38、HpP12、HpG27、Hpshi470 和 HpSJM180)的潜在药物靶点。将病原体幽门螺杆菌和宿主智人的基因组和代谢途径进行比较,并筛选出幽门螺杆菌特有的基因并进行分类。对这些独特的基因进行基因特性分析,以确定药物靶点的潜力。在不同幽门螺杆菌菌株中分析的总基因数中,HpB38、HpP12、HpG27、Hpshi470 和 HpSJM180 分别有 558、569、539、569 和 567 个基因被鉴定为独特分子,其中 17 个被鉴定为潜在的药物靶点。 hefABC 外排系统的膜融合蛋白、50S 核糖体蛋白 L33、氢化酶表达蛋白/形成 HypD、Cag 致病性岛蛋白 X、载脂蛋白 N 酰基转移酶、DNA 甲基转移酶、组蛋白样结合蛋白、肽聚糖相关脂蛋白 OprL 被认为是幽门螺杆菌的关键药物靶点。在预测的 17 个药物靶点中,有 3 个(hefABC 外排系统、氢化酶表达蛋白/形成 HypD、Cag 致病性岛蛋白 X)已经通过遗传或生化实验得到验证,这证明了我们的独特方法是有效的。