Quantifying rapid bacterial evolution and transmission within the mouse intestine

Kimberly S Vasquez; Lisa Willis; Nate J Cira; Katharine M Ng; Miguel F Pedro; Andrés Aranda-Díaz; Manohary Rajendram; Feiqiao Brian Yu; Steven K Higginbottom; Norma Neff; Gavin Sherlock; Karina B Xavier; Stephen R Quake; Justin L Sonnenburg; Benjamin H Good; Kerwyn Casey Huang

doi:10.1016/j.chom.2021.08.003

Quantifying rapid bacterial evolution and transmission within the mouse intestine

Cell Host Microbe. 2021 Sep 8;29(9):1454-1468.e4. doi: 10.1016/j.chom.2021.08.003. Epub 2021 Sep 1.

Authors

Kimberly S Vasquez¹, Lisa Willis², Nate J Cira², Katharine M Ng², Miguel F Pedro³, Andrés Aranda-Díaz², Manohary Rajendram², Feiqiao Brian Yu⁴, Steven K Higginbottom¹, Norma Neff⁴, Gavin Sherlock⁵, Karina B Xavier³, Stephen R Quake⁶, Justin L Sonnenburg⁷, Benjamin H Good⁸, Kerwyn Casey Huang⁹

Affiliations

¹ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
² Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
³ Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
⁴ Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
⁵ Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁶ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
⁷ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
⁸ Department of Physics, University of California at Berkeley, Berkeley, CA 94720, USA; Department of Applied Physics, Stanford University, Stanford, CA 94305, USA. Electronic address: bhgood@stanford.edu.
⁹ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: kchuang@stanford.edu.

Abstract

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.

Keywords: Escherichia coli; ciprofloxacin; cross-housing; gyrase; metabolism; metagenomics; motility; parallel evolution; population-genetics modeling; transmission.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology*
Ciprofloxacin / pharmacology*
DNA Barcoding, Taxonomic / methods*
Escherichia coli / drug effects
Escherichia coli / growth & development*
Escherichia coli / immunology
Evolution, Molecular
Gastrointestinal Microbiome / genetics*
Genetics, Population / methods
Germ-Free Life
Intestines / microbiology*
Mice
Selection, Genetic / genetics
Whole Genome Sequencing

Substances

Anti-Bacterial Agents
Ciprofloxacin

Abstract

Publication types

MeSH terms

Substances

Grants and funding