Microniches in the gastric glands control helicobacter pylori colonization of the stomach
Abstract/Contents
- Abstract
- Lifelong infection of the gastric mucosa by Helicobacter pylori can lead to peptic ulcers and gastric cancer. This bacterium resides in possibly the harshest niche in the human body, an organ which secretes liters of microbicidal acid, mucus, and digestive enzymes daily to aid in food digestion and to destroy ingested microbes. How is H. pylori able to survive in this harsh environment and persistently colonize their hosts for a lifetime? Previously, we reported that H. pylori can penetrate deep in the stomach mucosa and reside within a specialized compartment, or "microniche" in the gastric glands that contain epithelial precursor and stem cells. In this thesis, we investigated the significance of this microniche from the perspective of the microbe. We engineered isogenic, differentially-labeled H. pylori strains that we mixed and introduced into mice to understand the kinetics of how these gland-associated populations establish and spread, and to ask questions about intraspecies competition in these niches. Using 3D confocal microscopy and passive CLARITY technique (PACT), which renders tissues optically transparent, we mapped bacterial location within entire infected organs with unprecedented spatial resolution. We discovered that gland-associated populations do not intermix with free-swimming bacteria in the surface mucus. Rather, gland-associated H. pylori form stable clonal populations that compete for space and prevent newcomers from establishing in this specialized niche. Bacterial mutants unable to colonize the glands are outcompeted by wild-type strains. Additionally, we found that a combination of bacterial, host, and environmental factors control the density of these gland-associated populations. Collectively, our results show that the gastric glands provide a protective niche, or safe haven, for H. pylori to maintain a stable bacterial reservoir that likely replenishes the more transient populations in the surface mucus.
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 | Fung, Connie |
|---|---|
| Degree supervisor | Amieva, Manuel |
| Thesis advisor | Amieva, Manuel |
| Thesis advisor | Huang, Kerwyn Casey, 1979- |
| Thesis advisor | Monack, Denise M |
| Thesis advisor | Sonnenburg, Justin, 1973- |
| Degree committee member | Huang, Kerwyn Casey, 1979- |
| Degree committee member | Monack, Denise M |
| 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 | Connie Fung. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Connie Fung
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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