The intestinal microbiota controls intestinal salmonella infection
Abstract/Contents
- Abstract
- Salmonella enterica serovars are important human pathogens, leading to millions of infections and hundreds of thousands of deaths worldwide each year. Salmonella infection occurs by the fecal-oral route such that hosts are infected by ingesting contaminated food or water. The pathogen navigates the gastrointestinal tract and replicates to high levels in the distal intestinal site prior to transmission in the feces, where it can infect naïve hosts. Intestinal infection and pathogen transmission is a complex process that is likely controlled by a combination of host, environmental, and pathogen factors. This dissertation focuses on the role of the intestinal microbiota in intestinal Salmonella infection and transmission. Chapter 1 of this dissertation provides an overview of what is known about intestinal Salmonella infection and the role of the intestinal microbiota in this process. In Chapter 2 and 3, I utilize two strains of inbred mice with distinct intestinal Salmonella burdens and kinetics to dissect the role of the intestinal microbiota in intestinal Salmonella infection. Utilization of this system revealed that the composition of the intestinal microbiota dictates the level of Salmonella replication in the intestines and transmission in the feces. In Chapter 3, I identify Bacteroides spp. in resistant mice that mediate colonization resistance to intestinal Salmonella infection through production of the short-chain fatty acid propionate. In contrast, in Chapter 4 I identify Lachnospiraceae spp. present in susceptible mice that facilitate pathogen expansion, likely through the production of amino acids that Salmonella requires for intestinal growth. While host and environmental factors are crucial determinants of enteric infection outcome, pathogen factors are also important regulators of disease as well. Chapter 4 of this dissertation describes a novel surgical Salmonella infection model. In this model, the pathogen is injected directly into the distal intestine, allowing for genome-wide pathogen screens to identify pathogen factors required for colonization of the intestine. Taken together, this dissertation highlights the importance of the intestinal microbiota as a determinant of intestinal Salmonella disease severity and outcome, and advocates for the consideration of the intestinal microbiota as a therapeutic target for ameliorating intestinal infections. Chapter 5 of this dissertation reflects on current microbiota-targeting treatment strategies and future considerations for the development of microbiota-targeting therapies that reduce transmission of Salmonella and other enteric bacterial infections.
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 | 2018; ©2018 |
| Publication date | 2018; 2018 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Jacobson, Amanda Rose |
|---|---|
| Degree supervisor | Monack, Denise M |
| Thesis advisor | Monack, Denise M |
| Thesis advisor | Bhatt, Ami (Ami Siddharth) |
| Thesis advisor | Schneider, David (David Samuel) |
| Thesis advisor | Sonnenburg, Justin, 1973- |
| Degree committee member | Bhatt, Ami (Ami Siddharth) |
| Degree committee member | Schneider, David (David Samuel) |
| 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 | Amanda Rose Jacobson. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Amanda Rose Jacobson
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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