Salmonella exploits the intestinal microbiota to gain a competitive advantage in the mammalian gut
Abstract/Contents
- Abstract
- Foodborne bacterial pathogens cause approximately 3.6 million infections in the United States every year, with nontyphoidal Salmonella being the top pathogen responsible for most hospitalizations. While numerous studies have highlighted the importance of the intestinal microbiota in blocking these bacteria from colonizing the intestinal tract (known as 'colonization resistance'), little is known about what mechanisms pathogens use to overcome this resistance or how individual members of the microbiota might be inadvertently promoting such infections. This dissertation focuses on understanding how Salmonella enterica serovar Typhimurium interacts with the intestinal microbiota in order to colonize the mammalian gastrointestinal tract. In Chapter 1, I provide a general overview of what is known about Salmonella Typhimurium's biology and its interactions with the intestinal microbiota. As the gut is limited in nutrients and physical space, Salmonella is known to use various virulence strategies in order to disrupt the stability of the microbiota and create its own niche. In Chapter 2, I introduce the Type Six Secretion System (T6SS), a specialized secretion system utilized by certain Gram (-) bacteria for anti-prokaryotic and anti- eukaryotic purposes. While some bacteria switch their metabolism to utilize secondary nutrients to avoid metabolic competition in the gut, others opt to take a more direct approach and directly kill their competitors by secreting effectors via specific secretion systems such as the T6SS. In Chapter 3, I describe how Salmonella's anti-prokaryotic use of its T6SS impacts colonization in the gut. Finally, in Chapters 4 and 5, I probe how factors such as host- and microbial- derived metabolism impact pathogen establishment in the gut, and describe how providing mice a cholesterol-rich diet leads to Salmonella expansion in vivo. While Salmonella does not metabolize cholesterol itself, certain microbiota commensals can, resulting in a metabolic cross-feeding situation that appears to be spurring the pathogen's growth. Taken together, this dissertation highlights how Salmonella uses physical competition and metabolic exploitation in order to outcompete the intestinal microbiota, and describes potential mechanisms that could be therapeutically targeted in order to prevent future 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 | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Lugo, Kyler Alexander |
|---|---|
| Degree supervisor | Monack, Denise M |
| Thesis advisor | Monack, Denise M |
| Thesis advisor | Schneider, David |
| Thesis advisor | Sonnenburg, Justin, 1973- |
| Degree committee member | Schneider, David |
| 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 | Kyler Alexander Lugo |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Kyler Alexander Lugo
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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