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采用系统生物学方法探索大肠杆菌 O157:H7 的多药耐药性:基因相互作用网络。

Exploring the multi-drug resistance in Escherichia coli O157:H7 by gene interaction network: A systems biology approach.

机构信息

Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India.

Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India..

出版信息

Genomics. 2019 Jul;111(4):958-965. doi: 10.1016/j.ygeno.2018.06.002. Epub 2018 Jun 13.

Abstract

In the present study, we have constructed an interaction network of 29 antibiotic resistant genes along with 777 interactions in E. coli O157:H7. Gene ontology analysis reveals that 94, 89 and 67 genes have roles in the cellular process, biological process and molecular function respectively. Gene complexes related to tripartite efflux pumps mdtEF-tolC and ABC family efflux pump macAB-tolC play key roles in multidrug efflux systems. It is noteworthy to mention that, 19 genes are involved in multi-efflux pumps and they play a significant role in multidrug resistance (MDR); while 18 genes are vital for fatty acid synthesis. Interestingly, we found that the four genes arnABCD are involved in both MDR and in fatty acid synthesis. Hence these genes could be targeted for new drug discovery. On the whole, our results provide a detailed understanding of the mode of MDR mechanisms in E.coli O157:H7.

摘要

在本研究中,我们构建了大肠杆菌 O157:H7 中 29 种抗生素耐药基因及 777 种相互作用的互作网络。基因本体论分析表明,94、89 和 67 个基因分别在细胞过程、生物过程和分子功能中发挥作用。与三部分外排泵 mdtEF-tolC 和 ABC 家族外排泵 macAB-tolC 相关的基因复合物在外排泵系统中发挥关键作用。值得注意的是,19 个基因参与多外排泵,它们在多药耐药(MDR)中起重要作用;而 18 个基因对脂肪酸合成至关重要。有趣的是,我们发现 arnABCD 这四个基因既参与 MDR,又参与脂肪酸合成。因此,这些基因可能成为新药发现的靶点。总的来说,我们的结果提供了对大肠杆菌 O157:H7 中 MDR 机制模式的详细了解。

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