Singh Shailza, Malik B K, Sharma D K
Center for Energy Studies, Indian Institute of Technology Delhi, Hauz Khas, New Delhi-110016, India.
J Bioinform Comput Biol. 2007 Feb;5(1):135-53. doi: 10.1142/s0219720007002564.
The emergence of multidrug resistant varieties of Streptococcus pneumoniae (S. pneumoniae) has led to a search for novel drug targets. An in silico comparative analysis of metabolic pathways of the host Homo sapiens (H. sapiens) and the pathogen S. pneumoniae have been performed. Enzymes from the biochemical pathways of S. pneumoniae from the KEGG metabolic pathway database were compared with proteins from the host H. sapiens, by performing a BLASTp search against the non-redundant database restricted to the H. sapiens subset. The e-value threshold cutoff was set to 0.005. Enzymes, which do not show similarity to any of the host proteins, below this threshold, were filtered out as potential drug targets. Five pathways unique to the pathogen S. pneumoniae when compared to the host H. sapiens have been identified. Potential drug targets from these pathways could be useful for the discovery of broad-spectrum drugs. Potential drug targets were also identified from pathways related to lipid metabolism, carbohydrate metabolism, amino acid metabolism, energy metabolism, vitamin and cofactor biosynthetic pathways and nucleotide metabolism. Of the 161 distinct targets identified from these pathways, many are in various stages of progress at the Microbial Genome Database. However, 44 of the targets are new and can be considered for rational drug design. The study was successful in listing out potential drug targets from the S. pneumoniae proteome involved in vital aspects of the pathogen's metabolism, persistence, virulence and cell wall biosynthesis. This systematic evaluation of metabolic pathways of host and pathogen through reliable and conventional bioinformatics approach can be extended to other pathogens of clinical interest.
肺炎链球菌多重耐药菌株的出现促使人们寻找新的药物靶点。对宿主智人和病原体肺炎链球菌的代谢途径进行了计算机比较分析。通过对限于智人子集的非冗余数据库进行BLASTp搜索，将来自KEGG代谢途径数据库的肺炎链球菌生化途径中的酶与宿主智人的蛋白质进行比较。将e值阈值设定为0.005。低于此阈值且与任何宿主蛋白质均无相似性的酶被筛选出来作为潜在的药物靶点。已确定与宿主智人相比肺炎链球菌病原体特有的五条途径。这些途径中的潜在药物靶点可能有助于发现广谱药物。还从与脂质代谢、碳水化合物代谢、氨基酸代谢、能量代谢、维生素和辅因子生物合成途径以及核苷酸代谢相关的途径中确定了潜在的药物靶点。从这些途径中确定的161个不同靶点中，许多在微生物基因组数据库中处于不同的研究进展阶段。然而，其中44个靶点是新的，可用于合理药物设计。该研究成功列出了肺炎链球菌蛋白质组中涉及病原体代谢、存活、毒力和细胞壁生物合成等重要方面的潜在药物靶点。通过可靠且传统的生物信息学方法对宿主和病原体代谢途径进行的这种系统评估可扩展到其他具有临床意义的病原体。
