Influence of host cell biology on bacterial infection : listeria monocytogenes and the vascular endothelium
Abstract/Contents
- Abstract
- Vascular endothelial cells line the lumen of blood vessels and act as barrier that regulates the transport between the bloodstream and the underlying tissue. Thus, bacterial and viral pathogens that aim to reach such underlying tissue and cause infections distal to their initial site of entry must be able to subvert the barrier function of the vascular endothelium. We focus specifically on the bacterium Listeria monocytogenes, which has been shown to infect endothelial cells in vivo and exhibits myriad pathogenic strategies that contribute to its ability to travel from the initial site of infection, at the epithelial cells lining the small intestine, to distal organs such as the liver, spleen, brain, and placenta. We have developed culture-based models to study the molecular basis of L. monocytogenes infection of primary human endothelial cells (HUVEC). We have found that L. monocytogenes is directly internalized by endothelial cells in a phagocytosis-like process that is independent of bacterial invasion proteins and is regulated by Rho GTPase and the actin cytoskeleton, acting through focal adhesions and the formin family of actin nucleators. Further, we found that HUVEC display rapidly dynamic heterogeneity in susceptibility to such internalization; this heterogeneity results entirely from pre-existing HUVEC variability in susceptibility to L. monocytogenes adhesion and can be stabilized by perturbing cytoskeletal regulators. Finally, we developed an assay to examine how L. monocytogenes infected macrophages transfer bacteria directly to endothelial cells; surprisingly, and in contrast to direct invasion of bacteria, uptake of bacteria from infected macrophages is inhibited by actin polymerization in the recipient endothelial cell.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Rengarajan, Michelle |
|---|---|
| Associated with | Stanford University, Program in Biochemistry. |
| Primary advisor | Theriot, Julie |
| Thesis advisor | Theriot, Julie |
| Thesis advisor | Ferrell, James Ellsworth |
| Thesis advisor | Rohatgi, Rajat |
| Advisor | Ferrell, James Ellsworth |
| Advisor | Rohatgi, Rajat |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Michelle Rengarajan. |
|---|---|
| Note | Submitted to the Program in Biochemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Michelle Rengarajan
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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