Stereoselective Bacterial Metabolism of Antibiotics in Environmental Bacteria - A Novel Biochemical Workflow.

Stereoselective Bacterial Metabolism of Antibiotics in Environmental Bacteria - A Novel Biochemical Workflow.
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DOI:
10.3389/fmicb.2021.562157
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发表时间:
2021
影响因子:
5.2
通讯作者:
Kasprzyk-Hordern B
Kasprzyk-Hordern B
中科院分区:
生物学2区
文献类型:
--
作者:
Elder FCT;Feil EJ;Pascoe B;Sheppard SK;Snape J;Gaze WH;Kasprzyk-Hordern B

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尽管分子遗传学方法极大地增加了我们对抗生素耐药基因的进化和传播的理解,但关于抗生素-细菌(A-B)相互作用的动力学的研究较少,特别是关于立体化学。填补这一知识空白需要进行跨学科综合,并开发敏感和有选择性的分析工具。在这里,我们描述了SAM(立体选择性抗菌代谢)工作流程,一种新的跨学科方法,用于评估细菌耐药机制的背景下,A-B相互作用,利用全基因组测序和质谱法的组合。氯霉素用于提供概念验证,以证明耐药环境细菌的立体选择性代谢的重要性。我们的数据表明,氯霉素可以立体选择性地通过微生物代谢转化,R,R-(-)-CAP受到广泛的代谢转化的环境细菌菌株。相比之下,S,S-(+)-CAP不被该细菌菌株代谢,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缺乏先前暴露于该异构体。
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 R,R-(-)-CAP being subject to extensive metabolic transformation by an environmental bacterial strain. In contrast S,S-(+)-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.
DOI: 10.1099/mgen.0.000086
发表时间: 2016-09
期刊: Microbial genomics
影响因子: 3.9
作者:
Connor TR;Loman NJ;Thompson S;Smith A;Southgate J;Poplawski R;Bull MJ;Richardson E;Ismail M;Thompson SE;Kitchen C;Guest M;Bakke M;Sheppard SK;Pallen MJ
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DOI: 10.1021/acs.analchem.7b01527
发表时间: 2017-07-04
影响因子: 7.4
作者:
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通讯作者: Kasprzyk-Hordern, Barbara
DOI: 10.1371/journal.pcbi.1004557
发表时间: 2015-12
影响因子: 4.3
作者:
Kaminski J;Gibson MK;Franzosa EA;Segata N;Dantas G;Huttenhower C
通讯作者: Huttenhower C