Exploration of the regulatory networks of hybrid two-component systems in the model gut symbiont Bacteroides thetaiotaomicron

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This dissertation describes the regulatory capabilities of hybrid two-component systems in the model gut bacteria Bacteroides thetaiotaomicron. These unique proteins are important for carbohydrate sensing and consumption in the Bacteroides, but the full extent of their regulatory networks has not been previously explored. We created a chimeric hybrid two-component system that fused the well-characterized sensing domain of one, BT1754, to the uncharacterized regulatory domain of another, BT0366. We then used the BT1754 ligand, fructose, to functionally activate BT0366. Using genome-wide transcriptional profiling, we discovered that BT0366 both upregulates adjacent genes associated with the degradation of the plant polysaccharide arabinan, but also downregulates distal genes involved in mucin consumption. Using Chromatin Immunoprecipitation with high throughput sequencing, we then found that BT0366 binds directly to the genomic loci it helps regulate. Next, we developed tools for live-cell fluorescent microscopy of Bacteroides thetaiotaomicron in order to allow us to describe the physical positioning of hybrid two-component systems and their partnering molecules. This dissertation both describes regulatory activities of hybrid two-component systems in this common gut microbe and also provides tools for further study of subcellular localization in Bacteroides species.


Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2014
Issuance monographic
Language English


Associated with Lynch, Jonathan Braswell
Associated with Stanford University, Department of Microbiology and Immunology.
Primary advisor Sonnenburg, Justin, 1973-
Thesis advisor Sonnenburg, Justin, 1973-
Thesis advisor Amieva, Manuel
Thesis advisor Huang, Kerwyn Casey, 1979-
Thesis advisor Theriot, Julie
Advisor Amieva, Manuel
Advisor Huang, Kerwyn Casey, 1979-
Advisor Theriot, Julie


Genre Theses

Bibliographic information

Statement of responsibility Jonathan Braswell Lynch.
Note Submitted to the Department of Microbiology and Immunology.
Thesis Thesis (Ph.D.)--Stanford University, 2014.
Location electronic resource

Access conditions

© 2014 by Jonathan Braswell Lynch
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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