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基于基因组规模代谢模型寻找新型抗菌药物靶标基因

Genome-scale metabolic models as platforms for identification of novel genes as antimicrobial drug targets.

机构信息

Department of Microbiology & Biotechnology, Faculty of Science, Federal University Dutse, PMB 7156 Ibrahim Aliyu Bypass, Dutse, Jigawa State, Nigeria.

Department of Biotechnology and Medical Engineering, Faculty of Biosciences & Medical Engineering, Universiti Teknologi Malaysia, Johor Bahru 81310, Malaysia.

出版信息

Future Microbiol. 2018 Mar;13:455-467. doi: 10.2217/fmb-2017-0195. Epub 2018 Feb 22.

Abstract

The growing number of multidrug-resistant pathogenic bacteria is becoming a world leading challenge for the scientific community and for public health. However, advances in high-throughput technologies and whole-genome sequencing of bacterial pathogens make the construction of bacterial genome-scale metabolic models (GEMs) increasingly realistic. The use of GEMs as an alternative platforms will expedite identification of novel unconditionally essential genes and enzymes of target organisms with existing and forthcoming GEMs. This approach will follow the existing protocol for construction of high-quality GEMs, which could ultimately reduce the time, cost and labor-intensive processes involved in identification of novel antimicrobial drug targets in drug discovery pipelines. We discuss the current impact of existing GEMs of selected multidrug-resistant pathogenic bacteria for identification of novel antimicrobial drug targets and the challenges of closing the gap between genome-scale metabolic modeling and conventional experimental trial-and-error approaches in drug discovery pipelines.

摘要

越来越多的多药耐药病原菌正在成为科学界和公共卫生领域的一项全球性挑战。然而,高通量技术和病原菌全基因组测序的进步使得构建细菌基因组尺度代谢模型(GEM)变得越来越现实。使用 GEM 作为替代平台将加快利用现有的和即将推出的 GEM 来鉴定目标生物体内新型无条件必需基因和酶。这种方法将遵循构建高质量 GEM 的现有方案,这最终将减少在药物发现管道中鉴定新型抗菌药物靶标所涉及的时间、成本和劳动密集型过程。我们讨论了现有选定多药耐药病原菌 GEM 在鉴定新型抗菌药物靶标方面的当前影响,以及在药物发现管道中缩小基因组尺度代谢建模与传统实验试错方法之间差距的挑战。

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