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Genetic capitalism and stabilizing selection of antimicrobial resistance genotypes in Escherichia coli
Cladistics ( IF 3.6 ) Pub Date : 2020-06-29 , DOI: 10.1111/cla.12421
Colby T Ford 1, 2 , Gabriel Lopez Zenarosa 3 , Kevin B Smith 3 , David C Brown 1 , John Williams 1 , Daniel Janies 1
Affiliation  

Antimicrobial resistance (AMR) in pathogenic strains of bacteria, such as Escherichia coli (E. coli), adversely impacts personal and public health. In this study, we examine competing hypotheses for the evolution of AMR including (i) ‘genetic capitalism’ in which genotypes that confer antibiotic resistance are gained and not often lost in lineages, and (ii) ‘stabilizing selection’ in which genotypes that confer antibiotic resistance are gained and lost often. To test these hypotheses, we assembled a dataset that includes annotations for 409 AMR genotypes and a phylogenetic tree based on genome‐wide single nucleotide polymorphisms from 29 255 isolates of E. coli collected over the past 134 years. We used phylogenetic methods to count the times each AMR genotype was gained and lost across the tree and used model‐based clustering of the genotypes with respect to their gain and loss rates. We demonstrate that many genotypes cluster to support the hypothesis for genetic capitalism while a few genotypes cluster to support the hypothesis for stabilizing selection. Comparing the sets of genotypes that fall under each of the hypotheses, we found a statistically significant difference in the breakdown of resistance mechanisms through which the AMR genotypes function. The result that many AMR genotypes cluster under genetic capitalism reflects that strong positive selective forces, primarily induced by human industrialization of antibiotics, outweigh the potential fitness costs to the bacterial lineages for carrying the AMR genotypes. We expect genetic capitalism to further drive bacterial lineages to resist antibiotics. We find that antibiotics that function via replacement and efflux tend to behave under stabilizing selection and thus may be valuable in an antibiotic cycling strategy.

中文翻译:

大肠杆菌中的遗传资本主义和稳定选择抗菌素耐药性基因型

致病性细菌菌株(如大肠杆菌E. coli))中的抗菌素耐药性 (AMR) 会对个人和公共健康产生不利影响。在这项研究中,我们研究了 AMR 进化的竞争假设,包括(i)“遗传资本主义”,其中赋予抗生素抗性的基因型在谱系中获得并且不经常丢失,以及(ii)“稳定选择”,其中赋予抗生素抗性的基因型抗生素耐药性经常获得和失去。为了检验这些假设,我们组装了一个数据集,其中包括 409 个 AMR 基因型的注释和一个基于来自 29 255 个大肠杆菌分离株的全基因组单核苷酸多态性的系统发育树在过去的 134 年中收集。我们使用系统发育方法来计算每个 AMR 基因型在树中获得和丢失的时间,并使用基于模型的基因型聚类来衡量它们的增益和损失率。我们证明了许多基因型聚集以支持遗传资本主义的假设,而少数基因型聚集以支持稳定选择的假设。比较每个假设下的基因型组,我们发现 AMR 基因型发挥作用的抗性机制的分解存在统计学上的显着差异。许多 AMR 基因型在遗传资本主义下聚集的结果反映了强大的积极选择力量,主要由人类抗生素工业化诱导,超过携带 AMR 基因型的细菌谱系的潜在适应性成本。我们预计遗传资本主义将进一步推动细菌谱系抵抗抗生素。我们发现通过置换和外排发挥作用的抗生素往往在稳定选择下表现,因此在抗生素循环策略中可能很有价值。
更新日期:2020-06-29
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