ORCID ID
Graduation Date
Fall 12-17-2021
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Programs
Immunology, Pathology & Infectious Disease
First Advisor
Elizabeth A. Rucks
Abstract
Chlamydia trachomatis is a highly evolved obligate intracellular bacterial pathogen. During infection, organisms reside within a host epithelial cell in a membrane-bound vacuole called the inclusion. The inclusion membrane contains both pathogen and host components, including unique chlamydial type III effector proteins called Incs and host lipids like cholesterol and sphingomyelin. The inclusion membrane serves as the main barrier between the bacteria and the host cytosol, and thus, functions as the platform supporting host-chlamydial interactions. Via the inclusion membrane, C. trachomatis intercepts components of host vesicular traffic including many host SNARE proteins, which are a conserved family of eukaryotic proteins that function in membrane fusion and are important for chlamydial development. Therefore, we hypothesize that Chlamydia intercept specific SNARE proteins to reroute host vesicular trafficking pathways to the chlamydial inclusion for optimal chlamydial growth. We further hypothesize this is accomplished via transient interactions with chlamydial Inc proteins to maximize interactions with various subcellular compartments to diversify nutrient acquisition thus minimizing stress to the host cell. Hence, it is likely that chlamydial infection influences trafficking of proteins that are not directly recruited to the inclusion. To test this, we examined the localization and function of three eukaryotic SNARE proteins, VAMP3, VAMP4, and syntaxin 10, and one SNARE adapter protein, PICALM, in chlamydial infected cells. All four eukaryotic proteins localize to the chlamydial inclusion but are also found in vesicles throughout host cells. We found that VAMP3 dynamically interacts with multiple chlamydial inclusion membrane proteins during infection with C. trachomatis serovar L2. We further found that infection with C. trachomatis L2 expands VAMP4’s protein network but does not alter the protein network of syntaxin 10. Lastly, we identified the functions of VAMP3, VAMP4, and PICALM in host protein trafficking to chlamydial inclusions and found that PICALM and VAMP3 function similarly in transferrin recycling during infection with C. trachomatis serovar L2. These studies highlight the complex and dynamic nature of the interactions with host vesicular traffic occurring at the chlamydial inclusion for Chlamydia to establish and maintain their unique intracellular niche.
Recommended Citation
Jorgenson, Lisa M., "Understanding the Impact of Chlamydia Trachomatis Infection on Host Vesicular Trafficking" (2021). Theses & Dissertations. 601.
https://digitalcommons.unmc.edu/etd/601
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