ORCID ID
Graduation Date
Spring 5-9-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Programs
Immunology, Pathology & Infectious Disease
First Advisor
Stacey Gilk, PhD
Abstract
Coxiella burnetii, an obligate intracellular bacterium and the causative agent of the human disease Q fever, is still poorly understood in how it interacts within its host cell. Here, we explore the relationship between C. burnetii and the host transcription factor TFEB, the “master regulator” of lysosomal biogenesis, as well as the rest of the MiT/TFE family of proteins. The lysosome plays a critical role in the developmental cycle of C. burnetii, with its acidic environment necessary to activate bacterial metabolism and to serve as the initial niche for the C. burnetii-containing vacuole (CCV). While an initial acidic pH < 4.7 is essential to activate C. burnetii metabolism, the mature, growth-permissive CCV has a luminal pH of ~5.2 that remains stable throughout infection. Inducing CCV acidification to a lysosomal pH (~4.7) causes C. burnetii degradation. The results shown in this work demonstrate that TFEB acts primarily as a restrictive agent to C. burnetii growth and CCV size within the infected cell. It also characterizes how C. burnetii targets both lysosomal development and TFEB directly, using its T4BSS and effector proteins to reduce TFEB levels, inhibit TFEB phosphorylation, and restrict its nuclear translocation. This supports the hypothesis that C. burnetii blocks lysosomal biogenesis to prevent fusion of acidic lysosomes with the CCV. This, however, is not the full picture, as we also determined that TFEB plays a role in C. burnetii’s ability to reduce reactive oxygen species (ROS) levels in the host cell. We also demonstrated increased TFEB localization to the mitochondria. This leads us to hypothesize that C. burnetii reduces TFEB levels and regulates its localization within the cell, thereby inhibiting lysosomal development and restricting cellular ROS via the mitochondria.
Rights
The author holds the copyright to this work and any reuse or permissions must be obtained from the author directly.
Recommended Citation
Killips, Brigham, "Coxiella burnetii Modulates the Host Protein TFEB to Promote Infection" (2026). Theses & Dissertations. 1061.
https://digitalcommons.unmc.edu/etd/1061