Date of Award
5-2026
Degree Type
Thesis
Degree Name
Master of Science in Biomedical Sciences
First Advisor
Minal Mulye, PhD
Second Advisor
Ruth Borghaei, PhD
Third Advisor
Brian Balin, PhD
Abstract
Coxiella burnetii, an obligate intracellular bacterium and lung pathogen, infects and survives within mammalian macrophages, causing endocarditis years after initial infection. Coxiella manipulates macrophage lipid metabolism, particularly lipid storage organelles, lipid droplets (LDs), to persist long term in the mammalian host. The enzyme adipose triglyceride lipase (ATGL) initiates LD lipolysis, which is important for Coxiella growth. Breakdown of LDs results in production of the immunosuppressive lipid immune mediator, prostaglandin E2 (PGE2). Inhibition of ATGL and PGE2 production significantly impairs bacterial replication, suggesting the importance of ATGL-mediated lipolysis and PGE2 for Coxiella survival. Additionally, Coxiella growth is also dependent on the host transcription factor that regulates lipid metabolism, peroxisome proliferator-activated receptor α (PPARα). Overall, manipulation of lipid metabolism via ATGL, PGE2 and PPARα is important for support of Coxiella’s intracellular lifestyle, suggesting that treatment with lipid metabolism altering drugs might affect Coxiella growth as well. Glucagon-like peptide 1 receptor agonists (GLP- 1RAs), such as liraglutide and semaglutide, are widely used for the management of type II diabetes and obesity due to their ability to improve insulin sensitivity and promote lipolysis. GLP-1RAs activate the GLP-1 receptor (GLP-1R), which modulates lipid metabolism-associated genes and proteins, resulting in the breakdown of LDs. Since GLP-1RAs alter PPARα and ATGL expression in mammalian hosts, we hypothesize that GLP-1RA-mediated manipulation of lipid metabolism supports Coxiella burnetii growth in alveolar macrophages. To assess the importance of GLP-1RAs in Coxiella-infected cells, we measured bacterial growth in cells treated with GLP-1RA and liraglutide. Treatment with GLP-1RA and liraglutide increased Coxiella intracellular growth. Analysis revealed decreased atgl gene expression and PGE2 protein production in GLP- 1RA-treated Coxiella infected alveolar macrophages, suggesting alternative mechanisms exist to support Coxiella growth in GLP-1RA-treated cells. To identify other altered lipid metabolism and immune response genes that might support Coxiella growth, we performed TaqMan arrays. Genes associated with M2 macrophage polarization and lipid storage were significantly altered in Coxiella-infected cells after GLP-1RA treatment. Our studies indicate that GLP-1RA treatment shifts the macrophages towards the antiinflammatory M2 phenotype and induces lipid storage to create a permissive environment and support Coxiella intracellular growth. Future studies will continue to explore how GLP-1RAs support Coxiella growth and identify novel pathways that GLP-1RAs target in infected cells. Our study is the first to identifying the relationship between intracellular bacteria and GLP-1RAs, thus shedding light on the role of these widely used drugs during bacterial infections.
Recommended Citation
Novabilski, Sierra, "The Role of GLP-1R Agonists in Supporting Intracellular Bacterial Growth in Alveolar Macrophages" (2026). PCOM Biomedical Studies Student Scholarship. 259.
https://digitalcommons.pcom.edu/biomed/259