Novel Insights into Selection for Antibiotic Resistance in Complex Microbial Communities.
Novel Insights into Selection for Antibiotic Resistance in Complex Microbial Communities.
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DOI：
10.1128/mbio.00969-18
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发表时间：
2018-07-24
期刊：
影响因子：
6.4
通讯作者：
Gaze WH
中科院分区：
文献类型：
--
作者：
Murray AK;Zhang L;Yin X;Zhang T;Buckling A;Snape J;Gaze WH
最近的研究表明，在单一物种实验中，抗生素耐药性的选择发生在非常低的抗生素浓度下，但当物种嵌入复杂的微生物群落中时，这些发现的相关性尚不清楚。我们发现，在一个复杂的社区中，自然发生的耐药等位基因的选择强度保持不变，从低亚抑制到临床相关浓度。选择增加抗生素浓度达到一个平台之前，选择保持恒定的2个数量级的浓度范围。这可能是由于在耐药菌群快速降解细胞外抗生素后，群落中敏感细菌的交叉保护作用，通过化学定量和细菌生长实验的组合实验显示。在头孢噻肟暴露下进化的污水来源的细菌群落的宏基因组和16 S rRNA分析显示，blaCTX-M基因优先富集于所有其他β-内酰胺酶基因，以及抗生素耐药的机会致病菌的正选择和共选择。这些发现对我们理解抗生素耐药性的演变具有深远的影响，挑战了长期以来的假设，即选择以剂量依赖的方式发生。抗生素耐药性是社会面临的最大全球性问题之一。尽管如此，人们对在非常低的抗生素浓度下进行抗性选择的情况知之甚少。我们表明，在一个复杂的细菌群落中，临床上重要的耐药基因的选择强度可以在一个大的抗生素浓度范围内保持恒定（宽的选择空间）。因此，在很大程度上研究不足的生态区室可能是一样重要的临床环境的抗生素耐药性的选择。
Recent research has demonstrated that selection for antibiotic resistance occurs at very low antibiotic concentrations in single-species experiments, but the relevance of these findings when species are embedded in complex microbial communities is unclear. We show that the strength of selection for naturally occurring resistance alleles in a complex community remains constant from low subinhibitory to above clinically relevant concentrations. Selection increases with antibiotic concentration before reaching a plateau where selection remains constant over a 2-order-magnitude concentration range. This is likely to be due to cross protection of the susceptible bacteria in the community following rapid extracellular antibiotic degradation by the resistant population, shown experimentally through a combination of chemical quantification and bacterial growth experiments. Metagenome and 16S rRNA analyses of sewage-derived bacterial communities evolved under cefotaxime exposure show preferential enrichment for blaCTX-M genes over all other beta-lactamase genes, as well as positive selection and co-selection for antibiotic resistant, opportunistic pathogens. These findings have far-reaching implications for our understanding of the evolution of antibiotic resistance, by challenging the long-standing assumption that selection occurs in a dose-dependent manner. Antibiotic resistance is one of the greatest global issues facing society. Still, comparatively little is known about selection for resistance at very low antibiotic concentrations. We show that the strength of selection for clinically important resistance genes within a complex bacterial community can remain constant across a large antibiotic concentration range (wide selective space). Therefore, largely understudied ecological compartments could be just as important as clinical environments for selection of antibiotic resistance.