Eating the Fat of the Land: The Work of Coxiella burnetii To Traverse Intracellular Lipid Landscapes
Graduation Date
Spring 2025
Document Type
Thesis
Degree Name
Master of Science (MS)
Programs
Medical Anatomy
First Advisor
Megan Perry
Second Advisor
Samantha Simet
Third Advisor
Travis McCumber
Fourth Advisor
Stacey Gilk
Abstract
Coxiella burnetii is an obligate intracellular pathogen and the causative agent of Q fever in humans. With primary hosts in livestock ruminants, C. burnetii is endemic globally, presenting significant health risks to agricultural workers and herd health at large. Numerous wild animal reservoirs exist, increasingly threatened by expanding livestock ranges. Furthermore, with a low infectious dose through aerosol transmission, the CDC considers C. burnetii a potential bioweapon, though in humans a large amount of infections persist subclinically, occasionally progressing to pneumonia and hepatitis with chronic infections leading to endocarditis.
The parasitic life cycle of C. burnetii is biphasic, a small cell variant gains entry into the host cell, assembling a parasitic vacuole by fusing with vesicles along the endosome/lysosome continuum, with the bacterium expanding into a large cell variant for replication and manipulation of the host environment. The vacuole assembled by C. burnetii is uniquely acidic, utilizing a Type IVb secretion system (T4BSS) for its parasitic goals. A protein secreted by the T4BSS is CbEPF1, singled out for its FFAT motif, implicating it in membrane contact sites through interaction with endogenous VAP-family proteins. HeLa cells transfected with CbEPF1 feature an increased number of lipid droplets of larger diameter. On a subcellular level, CbEPF1 localizes to budding lipid droplets, continuing to stay associated with LDs entering their cytosolic stage. These EPF1 studded lipid droplets form membrane contact sites with the endoplasmic reticulum, hinting at mechanisms in manipulating host lipid metabolism.
Recommended Citation
Porto, Charlie, "Eating the Fat of the Land: The Work of Coxiella burnetii To Traverse Intracellular Lipid Landscapes" (2025). Theses & Dissertations. 926.
https://digitalcommons.unmc.edu/etd/926
Comments
2025 Copyright, the authors