Influence of host cell biology on bacterial infection : listeria monocytogenes and the vascular endothelium

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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.


Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2016
Issuance monographic
Language English


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


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

© 2016 by Michelle Rengarajan
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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