Elder Felicity C T, Feil Edward J, Pascoe Ben, Sheppard Samuel K, Snape Jason, Gaze William H, Kasprzyk-Hordern Barbara
Department of Chemistry, University of Bath, Bath, United Kingdom.
The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Front Microbiol. 2021 Apr 16;12:562157. doi: 10.3389/fmicb.2021.562157. eCollection 2021.
Although molecular genetic approaches have greatly increased our understanding of the evolution and spread of antibiotic resistance genes, there are fewer studies on the dynamics of antibiotic - bacterial (A-B) interactions, especially with respect to stereochemistry. Addressing this knowledge gap requires an interdisciplinary synthesis, and the development of sensitive and selective analytical tools. Here we describe SAM (stereoselective antimicrobial metabolism) workflow, a novel interdisciplinary approach for assessing bacterial resistance mechanisms in the context of A-B interactions that utilise a combination of whole genome sequencing and mass spectrometry. Chloramphenicol was used to provide proof-of-concept to demonstrate the importance of stereoselective metabolism by resistant environmental bacteria. Our data shows that chloramphenicol can be stereoselectively transformed via microbial metabolism with CAP being subject to extensive metabolic transformation by an environmental bacterial strain. In contrast +)CAP is not metabolised by this bacterial strain, possibly due to the lack of previous exposure to this isomer in the absence of historical selective pressure to evolve metabolic capacity.
尽管分子遗传学方法极大地增进了我们对抗生素抗性基因的进化和传播的理解，但关于抗生素 - 细菌（A - B）相互作用动态的研究较少，尤其是在立体化学方面。弥补这一知识空白需要跨学科的综合研究以及开发灵敏和选择性的分析工具。在这里，我们描述了SAM（立体选择性抗菌代谢）工作流程，这是一种新颖的跨学科方法，用于在A - B相互作用的背景下评估细菌抗性机制，该方法结合了全基因组测序和质谱技术。使用氯霉素来提供概念验证，以证明抗性环境细菌的立体选择性代谢的重要性。我们的数据表明，氯霉素可通过微生物代谢进行立体选择性转化，其中氯霉素（CAP）会受到一种环境细菌菌株的广泛代谢转化。相比之下，（+）CAP不会被该细菌菌株代谢，这可能是由于在缺乏进化代谢能力的历史选择压力的情况下，该细菌菌株此前未接触过这种异构体。
