Genome-Wide Identification of Potential Drug Target in Enterobacteriaceae Family: A Homology-Based Method
Genome-Wide Identification of Potential Drug Target in Enterobacteriaceae Family: A Homology-Based Method
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DOI：
10.1089/mdr.2016.0259
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发表时间：
2018-01-01
影响因子：
2.6
通讯作者：
Sohrabi, Seyyed Mohsen
中科院分区：
文献类型：
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作者：
Hadizadeh, Morteza;Tabatabaiepour, Seyyede Nasim;Sohrabi, Seyyed Mohsen
肠杆菌科是革兰氏阴性、兼性厌氧、不形成孢子的杆状细菌的大家族，其包括无害和致病生物。肠杆菌科细菌耐药性的出现和发展使严重感染的治疗变得复杂。本研究的目的是采用基于同源性的计算方法预测和表征肠杆菌科中推定的药物靶标。通过细胞功能预测、亚细胞定位预测、广谱性和可药性分析对最终推定的药物靶点进行定性表征。在分析的6，327个蛋白质中，选择35个蛋白质作为肠杆菌科中的最终推定药物靶标。这些推定的药物靶点涉及不同的重要途径，如代谢、大分子生物合成和细胞分裂。预测的药物靶点也定位于病原体的细胞质和细胞质膜中，作为抗菌剂或疫苗靶点。在35个药物靶点中，5个靶点可作为药物靶点，30个靶点不可作为药物靶点，可作为新的药物靶点，有待进一步评价以开发新的抗菌药物。13种药物靶标被认为是广谱靶标。预期我们的研究结果可以促进新型抗菌剂的生产，用于有效治疗由肠杆菌科病原体引起的感染。
The Enterobacteriaceae is a large family of Gram-negative, facultative anaerobic, non-spore forming rod-shaped bacteria that includes harmless and pathogenic organisms. The emergence and development of drug resistance in Enterobacteriaceae is complicating the treatment of serious infections. The aim of this study is to predict and characterize putative drug targets in Enterobacteriaceae family employing a homology-based computational method. The final putative drug targets were qualitatively characterized via cellular function prediction, subcellular localization prediction, broad-spectrum, and druggability analyses. Of 6,327 analyzed proteins, 35 proteins were selected as final putative drug targets in Enterobacteriaceae family. These putative drug targets were involved in different vital pathways like metabolism, biosynthesis of macromolecule, and cell division. Predicted drug targets were also localized in the cytoplasm and cytoplasmic membrane of the pathogen that acts as antimicrobial or vaccine targets. Of 35 drug targets, 5 targets were druggable and 30 targets were not druggable and were predicted as novel drug targets, which should be further evaluated to develop new antimicrobial. Thirteen drug targets were considered as broad-spectrum targets. It is expected that results of our study could facilitate the production of novel antibacterial for efficient treatment of infections caused by Enterobacteriaceae pathogens.