Sakharkar Kishore R, Sakharkar Meena K, Chow Vincent T K
BioInformatics Institute, Singapore.
In Silico Biol. 2004;4(3):355-60.
Complete genome sequences of several pathogenic bacteria have been determined, and many more such projects are currently under way. While these data potentially contain all the determinants of host-pathogen interactions and possible drug targets, computational tools for selecting suitable candidates for further experimental analyses are currently limited. Detection of bacterial genes that are non-homologous to human genes, and are essential for the survival of the pathogen represents a promising means of identifying novel drug targets. We have used three-way genome comparisons to identify essential genes from Pseudomonas aeruginosa. Our approach identified 306 essential genes that may be considered as potential drug targets. The resultant analyses are in good agreement with the results of systematic gene deletion experiments. This approach enables rapid potential drug target identification, thereby greatly facilitating the search for new antibiotics. These results underscore the utility of large genomic databases for in silico systematic drug target identification in the post-genomic era.
几种致病细菌的全基因组序列已被测定，目前还有更多此类项目正在进行中。虽然这些数据可能包含宿主与病原体相互作用的所有决定因素以及可能的药物靶点，但目前用于选择合适候选对象进行进一步实验分析的计算工具有限。检测与人类基因非同源且对病原体生存至关重要的细菌基因，是识别新型药物靶点的一种有前景的方法。我们利用三方基因组比较从铜绿假单胞菌中鉴定出必需基因。我们的方法鉴定出了306个可能被视为潜在药物靶点的必需基因。所得分析结果与系统性基因缺失实验的结果高度一致。这种方法能够快速识别潜在的药物靶点，从而极大地促进新型抗生素的寻找。这些结果强调了大型基因组数据库在基因组时代进行计算机辅助系统性药物靶点识别中的实用性。
