Quantifying rapid bacterial evolution and transmission within the mouse intestine

• Published in: Cell host & microbe Vol. 29; no. 9; pp. 1454 - 1468.e4
• Main Authors: Vasquez, Kimberly S., Willis, Lisa, Cira, Nate J., Ng, Katharine M., Pedro, Miguel F., Aranda-Díaz, Andrés, Rajendram, Manohary, Yu, Feiqiao Brian, Higginbottom, Steven K., Neff, Norma, Sherlock, Gavin, Xavier, Karina B., Quake, Stephen R., Sonnenburg, Justin L., Good, Benjamin H., Huang, Kerwyn Casey
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.09.2021
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; ciprofloxacin; Ciprofloxacin - pharmacology; cross-housing; DNA Barcoding, Taxonomic - methods; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - growth & development; Escherichia coli - immunology; Evolution, Molecular; Gastrointestinal Microbiome - genetics; Genetics, Population - methods; Germ-Free Life; gyrase; Intestines - microbiology; metabolism; metagenomics; Mice; motility; parallel evolution; population-genetics modeling; Selection, Genetic - genetics; transmission; Whole Genome Sequencing; parallel evolution; gyrase; transmission; Escherichia coli; metagenomics; cross-housing; motility; metabolism; population-genetics modeling; ciprofloxacin
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2021.08.003

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. Mutations in genes involved in motility and metabolite utilization are reproducibly selected within days. Even with rapid selection, coprophagy enforced similar barcode distributions across co-housed mice. Whole-genome sequencing of hundreds of isolates revealed linked alleles that demonstrate between-host transmission. A population-genetics model predicts substantial fitness advantages for certain mutants and that migration accounted for ∼10% of the resident microbiota each day. Treatment with ciprofloxacin suggests 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. [Display omitted] •DNA barcodes allow tracking of bacterial strain-level dynamics in the mouse gut•Mutations in motility and metabolic genes are reproducibly selected for within days•A population-genetics model predicts a bacterial migration rate of >10% per day•Ciprofloxacin treatment decreases strain diversity and stimulates transmission Vasquez et al. demonstrate the effectiveness of DNA barcodes for quantifying bacterial intra-species colonization dynamics, selection, and transmission in the mammalian gut and the effects of antibiotic treatment. In combination with a population-genetics model, the migration rate of gut bacteria is estimated to be ∼10% per day.