Date of Submission

7-2025

Document Type

Thesis

Degree Name

Master of Science in Cellular and Molecular Biology

Department

Biology and Environmental Sciences

Advisor

Eva Sapi, Ph.D.

Committee Member

Alireza G. Senejani, Ph.D.

Committee Member

J. Michael Sellers

Keywords

Lyme Disease, Borrelia Burgdorferi, Actin Cytoskeleton, Bacterial Invasion, Breast Cancer cells, Actin Inhibitors

MeSH

Borrelia burgdorferi, Lyme Disease, Actin Cytoskeleton, Breast Neoplasms, Cytochalasin D

LCSH

Borrelia burgdorferi, Lyme disease, Breast—Cancer, Actin

Abstract

Lyme disease, caused by the spirochete Borrelia burgdorferi, is an emerging health concern in the United States and beyond. While primarily known as a tick-borne pathogen, recent studies have reported the presence of B. burgdorferi in breast cancer tissues, including those with poor prognosis and is capable of invading both normal and neoplastic epithelial cells by hijacking host cellular processes. Studies suggest that a critical mechanism facilitating this invasion is the remodeling of the actin cytoskeleton. Actin filaments are essential for maintaining cell shape, enabling motility, and mediating endocytosis and phagocytosis. Given these essential functions, actin filaments have become key targets for pharmacological inhibitors in host-pathogen interaction studies. While evidence supports the role of actin inhibitors in preventing bacterial entry, the specific impact of B. burgdorferi on neoplastic epithelial cells remains unclear. This raised a key question: can actin inhibitors limit B. burgdorferi invasion into neoplastic epithelial cells? Hence, this study utilized two well-characterized actin inhibitors, Cytochalasin D and Latrunculin A, to investigate whether altering the cytoskeletal could limit bacterial invasion. The MDA-MB-231 mammary breast cancer cell line was used as a working model to investigate the impact of actin inhibitors, administered as single and daily doses. Cells infected with B. burgdorferi were evaluated using quantitative real-time PCR targeting the 16S rRNA gene at multiple time points (up to 72 hours), followed by immunofluorescence to assess actin filament structure and bacterial localization. Results showed approximately 20%–25% reduction in bacterial levels, with disrupted actin organization and decreased invasion in treated cells. These findings highlight the importance of actin integrity in facilitating B. burgdorferi invasion into breast cancer cells and further targeting this host mechanism may offer a potential strategy to limit infections associated with tumor progression.

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