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Quantifying the interplay between rapid bacterial evolution within the mouse intestine and transmission between hosts
bioRxiv - Microbiology Pub Date : 2020-12-05 , DOI: 10.1101/2020.12.04.412072
Kimberly S. Vasquez , Lisa Willis , Nate Cira , Katharine M. Ng , Miguel F. Pedro , Andrés Aranda-Díaz , Manohary Ranjendram , Feiqiao Brian Yu , Steven K. Higginbottom , Norma Neff , Gavin Sherlock , Karina B. Xavier , Stephen Quake , Justin Sonnenburg , Benjamin H. Good , Kerwyn Casey Huang

Due to limitations on high-resolution strain tracking, selection dynamics during gut-microbiota colonization and transmission between hosts remain mostly mysterious. Here, we introduced hundreds of barcoded Escherichia coli strains into germ-free mice and quantified strain-level dynamics and metagenomic changes. Mutants involved in motility and utilization of abundant metabolites were reproducibly selected within days. Even with rapid selection, coprophagy enforced similar barcode distributions across co-housed mice. Whole-genome sequencing of hundreds of isolates quantified evolutionary dynamics and revealed linked alleles. A population-genetics model predicted substantial fitness advantages for certain mutants and that migration accounted for ~10% of the resident microbiota each day. Treatment with ciprofloxacin demonstrated the interplay between selection and transmission. While initial colonization was mostly uniform, in two mice a bottleneck reduced diversity and selected for ciprofloxacin resistance in the absence of drug. These findings highlight the interplay between environmental transmission and rapid, deterministic selection during evolution of the intestinal microbiota.

中文翻译:

量化小鼠肠道内细菌快速进化与宿主之间传播之间的相互作用

由于高分辨率菌株追踪的局限性,肠道菌群定植和寄主之间传播期间的选择动力学大多仍然是神秘的。在这里,我们将数百种带有条形码的大肠杆菌菌株引入无菌小鼠中,并对菌株水平的动力学和宏基因组学变化进行了量化。在几天之内就可重现地选择涉及活力和丰富代谢物利用的突变体。即使进行快速选择,共同宣传也会在共同饲养的小鼠中强制执行类似的条形码分布。数百个分离株的全基因组测序定量了进化动力学并揭示了相关的等位基因。群体遗传模型预测某些突变体具有显着的适应性优势,并且每天迁移约占常驻菌群的10%。环丙沙星治疗证明了选择和传播之间的相互作用。虽然最初的定居大多是统一的,但在两只小鼠中,瓶颈降低了多样性,并在不存在药物的情况下选择了环丙沙星耐药性。这些发现强调了肠道菌群进化过程中环境传播与快速,确定性选择之间的相互作用。
更新日期:2020-12-05
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