Quantitative analysis of Listeria monocytogenes invasion and spread in epithelial cells
Abstract/Contents
- Abstract
- Together, epithelial cells create the intestinal epithelium, a selectively permeable barrier that is the home and target of many microbes. One such microbe is the ubiquitous foodborne pathogen Listeria monocytogenes, which breaches the intestinal epithelium during an oral infection. L. monocytogenes first invades the cytoplasm of a host epithelial cell, which allows the bacterium to polymerize actin and create comet tails to drive its own motility and spread to neighboring epithelial cells. In this work, we focus on two steps of the L. monocytogenes intracellular life cycle: invasion and cell-to-cell spread. First, we demonstrate that the canonical receptor E-cadherin, which creates a physical link between the bacterium and filamentous actin, serves primarily as an adhesive to mediate invasion. Indeed, the minimum requirement for bacterial invasion is the presence of the extracellular domain of E-cadherin. Next, we show by simulation and live microscopy that L. monocytogenes cell-to-cell spread is heterogeneous as it proceeds by way of two populations: local spreaders and pioneers. Our data support the model that pioneers spread directly to non-neighboring cells via long bacterial-mediated host cell protrusions tens of microns long. We also use simulations to show that the combination of local spreaders and pioneers allows L. monocytogenes to more successfully create a persistent infection in the intestinal epithelium. Finally, we explore the use of human intestinal enteroids as a new model system to study L. monocytogenes pathogenesis in intestinal epithelial cells. Specifically, we show that L. monocytogenes can invade human enteroids via a mechanism independent of E-cadherin/internalin A, which differs from findings made in transformed epithelial cell lines.
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 | Ortega, Fabian Ernesto |
|---|---|
| Degree supervisor | Theriot, Julie |
| Thesis advisor | Theriot, Julie |
| Thesis advisor | Amieva, Manuel |
| Thesis advisor | Rohatgi, Rajat |
| Thesis advisor | Yeh, Ellen |
| Degree committee member | Amieva, Manuel |
| Degree committee member | Rohatgi, Rajat |
| Degree committee member | Yeh, Ellen |
| Associated with | Stanford University, Department of Biochemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Fabian Ernesto Ortega. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Fabian Ernesto Ortega
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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