Multiomics reveals critical metabolites for colonization of salmonella in superspreaders hosts
Abstract/Contents
- Abstract
- The molecular understanding of host-pathogen interactions in the GI tract of superspreader hosts is incomplete. In a mouse model of chronic, asymptomatic Salmonella enterica serovar Typhimurium (S. Tm) infection, we performed untargeted metabolomics on the feces of mice and found superspreader hosts possess distinct metabolic signatures compared to non-superspreaders, including differential levels of L-arabinose. RNA-seq on S. Tm in superspreader fecal samples showed increased expression of the L-arabinose catabolism pathway in vivo. By combining bacterial genetics and diet manipulation, we demonstrate that diet-derived L-arabinose provides S. Tm a competitive advantage in the GI tract. We show that the expansion of S. Tm in the GI tract requires a previously uncharacterized alpha-N-arabinofuranosidase that can liberate L-arabinose from dietary polysaccharides. Ultimately, we demonstrate that pathogen-liberated L-arabinose from the diet provides a competitive advantage to S. Tm in vivo. These findings propose L-arabinose as a critical driver of S. Tm expansion in the GI tracts of superspreader hosts.
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 | Ruddle, Sarah |
|---|---|
| Degree supervisor | Monack, Denise M |
| Thesis advisor | Monack, Denise M |
| Thesis advisor | Bhatt, Ami (Ami Bharat) |
| Thesis advisor | Bollyky, Paul |
| Thesis advisor | Sonnenburg, Justin, 1973- |
| Degree committee member | Bhatt, Ami (Ami Bharat) |
| Degree committee member | Bollyky, Paul |
| 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 | Sarah Ruddle. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/wp272jc2042 |
Access conditions
- Copyright
- © 2022 by Sarah Ruddle
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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