Cardona Silvia T, Selin Carrie, Gislason April S
a Department of Microbiology , University of Manitoba , Winnipeg , Canada and.
b Department of Medical Microbiology & Infectious Disease , University of Manitoba , Winnipeg , Canada.
Crit Rev Microbiol. 2015;41(4):465-72. doi: 10.3109/1040841X.2013.866073. Epub 2014 Mar 12.
The increasing emergence of antimicrobial multiresistant bacteria is of great concern to public health. While these bacteria are becoming an ever more prominent cause of nosocomial and community-acquired infections worldwide, the antibiotic discovery pipeline has been stalled in the last few years with very few efforts in the research and development of novel antibacterial therapies. Some of the root causes that have hampered current antibiotic drug development are the lack of understanding of the mode of action (MOA) of novel antibiotic molecules and the poor characterization of the bacterial physiological response to antibiotics that ultimately causes resistance. Here, we review how bacterial genetic tools can be applied at the genomic level with the goal of profiling resistance to antibiotics and elucidating antibiotic MOAs. Specifically, we highlight how chemical genomic detection of the MOA of novel antibiotic molecules and antibiotic profiling by next-generation sequencing are leveraging basic antibiotic research to unprecedented levels with great opportunities for knowledge translation.
抗菌多重耐药细菌的不断出现引起了公共卫生领域的高度关注。虽然这些细菌已日益成为全球医院感染和社区获得性感染的一个更为突出的原因，但在过去几年中，抗生素研发渠道一直停滞不前，新型抗菌疗法的研发投入极少。阻碍当前抗生素药物研发的一些根本原因包括对新型抗生素分子的作用模式（MOA）缺乏了解，以及对最终导致耐药性的细菌对抗生素的生理反应缺乏充分表征。在此，我们综述如何在基因组水平应用细菌遗传学工具，以对抗生素耐药性进行分析并阐明抗生素的作用模式。具体而言，我们强调新型抗生素分子作用模式的化学基因组学检测以及通过下一代测序进行抗生素分析如何将基础抗生素研究提升到前所未有的水平，并为知识转化带来巨大机遇。
