Neelapu Nageswara R R, Mutha Naresh V R, Akula Srinivas
Department of Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam-530045. AP, India.
Infect Disord Drug Targets. 2015;15(2):106-17. doi: 10.2174/1871526515666150724111528.
Helicobacter pylori colonizes the stomach, causing gastritis, peptic ulcers and gastric carcinoma. Drugs for treatment of H. pylori relieve from gastritis or pain but are not specific to H. pylori. Therefore, there is an immediate requirement for new therapeutic molecules to treat H. pylori. Current study investigates identification of drug targets in the strain HPAG1 of H. pylori by in silico genome analysis. Genome of HPAG1 was reconstructed for metabolic pathways and compared with Homosapien sapiens to identify genes which are unique to H. pylori. 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 H. pylori strain HPAG1, nearly 542 genes qualified as unique molecules and among them 29 were identified to be potential drug targets. Co/Zn/Cd efflux system membrane fusion protein, Ferric sidephore transport system and biopolymer transport protein EXbB were found to be critical drug targets to H. pylori HPAG1. Five genes (superoxide dismutase, HtrA protease/chaperone protein, Heatinducible transcription repressor HrcA, HspR, transcriptional repressor of DnaK operon, Cobalt-zinccadmium resistance protein CzcA) of the 29 predicted drug targets are already experimentally validated either genetically or biochemically lending credence to our unique approach.
幽门螺杆菌寄居于胃部,可引发胃炎、消化性溃疡及胃癌。用于治疗幽门螺杆菌的药物可缓解胃炎或疼痛,但并非针对幽门螺杆菌具有特异性。因此,迫切需要新的治疗分子来治疗幽门螺杆菌。当前研究通过计算机基因组分析来探究幽门螺杆菌菌株HPAG1中的药物靶点。对HPAG1的基因组进行代谢途径重建,并与智人进行比较,以鉴定幽门螺杆菌特有的基因。对这些独特基因进行基因特性分析,以确定药物靶点的潜力。在幽门螺杆菌菌株HPAG1分析的基因总数中,近542个基因被鉴定为独特分子,其中29个被确定为潜在的药物靶点。发现钴/锌/镉外排系统膜融合蛋白、铁载体转运系统和生物聚合物转运蛋白EXbB是幽门螺杆菌HPAG1的关键药物靶点。29个预测的药物靶点中的5个基因(超氧化物歧化酶、HtrA蛋白酶/伴侣蛋白、热诱导转录阻遏物HrcA、HspR,DnaK操纵子的转录阻遏物、钴-锌-镉抗性蛋白CzcA)已经通过遗传学或生物化学实验验证,这为我们独特的方法提供了可信度。