Mapping colonization dynamics and evolution within the mammalian host
Abstract/Contents
- Abstract
- The gut microbiome has been shown to be pivotal in maintaining host health through many different avenues such as immune regulation, pathogen resistance, and metabolism. Continued improvement in tool development has led to the discovery of the importance of both the identity of the species present and also the genetic variation and abundances of genetically distinct subpopulations within a host over time. Due to limitations on high-resolution strain tracking, selection dynamics during gut-microbiota colonization and transmission between hosts have remained mostly mysterious. In my thesis, we individually introduced barcoded Escherichia coli and Bacteroides thetaiotaomicron strains into germ-free mice and quantified strain-level dynamics and genetic changes. Mutations in genes involved in motility and metabolite utilization were reproducibly selected within days. Even with rapid selection, coprophagy generally 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 ~1-10% the E. coli in the resident microbiota each day, but much lower fractions for B. thetaiotaomicron. Treatment with ciprofloxacin suggests interplay between selection and transmission. These findings highlight the interplay between environmental transmission and rapid, deterministic selection during evolution of the intestinal microbiota.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Vasquez, Kimberly Stefany |
|---|---|
| Degree supervisor | Huang, Kerwyn Casey, 1979- |
| Thesis advisor | Huang, Kerwyn Casey, 1979- |
| Thesis advisor | Monack, Denise M |
| Thesis advisor | Sherlock, Gavin |
| Thesis advisor | Sonnenburg, Justin, 1973- |
| Degree committee member | Monack, Denise M |
| Degree committee member | Sherlock, Gavin |
| Degree committee member | Sonnenburg, Justin, 1973- |
| Associated with | Stanford University, Department of Microbiology and Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Kimberly Stefany Vasquez. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/xz103wg1578 |
Access conditions
- Copyright
- © 2022 by Kimberly Stefany Vasquez
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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