Hadizadeh Morteza, Tabatabaiepour Seyyede Nasim, Tabatabaiepour Seyyede Zahra, Hosseini Nave Hossein, Mohammadi Mohsen, Sohrabi Seyyed Mohsen
1 Department of Agriculture, Payame Noor University (PNU) , Tehran, Iran .
2 Faculty of Agriculture, Department of Plant Breeding and Biotechnology, Shahed University , Tehran, Iran .
Microb Drug Resist. 2018 Jan/Feb;24(1):8-17. doi: 10.1089/mdr.2016.0259. Epub 2017 May 18.
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.
肠杆菌科是一大类革兰氏阴性、兼性厌氧、不形成芽孢的杆状细菌,包括无害菌和致病菌。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的潜在药物靶点。通过细胞功能预测、亚细胞定位预测、广谱性和可成药性分析对最终的潜在药物靶点进行定性表征。在分析的6327种蛋白质中,有35种蛋白质被选为肠杆菌科的最终潜在药物靶点。这些潜在药物靶点参与了不同的重要途径,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在病原体的细胞质和细胞质膜中,可作为抗菌或疫苗靶点。在35个药物靶点中,5个靶点是可成药的,30个靶点不可成药,被预测为新型药物靶点,应进一步评估以开发新的抗菌药物。13个药物靶点被认为是广谱靶点。预计我们的研究结果将有助于生产新型抗菌药物,以有效治疗由肠杆菌科病原体引起的感染。