Date of Submission

12-2025

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

Saumya Ramanathan, Ph.D.

Keywords

Bacterial Infections, Borrelia Burgdorferi, Epithelial Cells, Cell Proliferation, Immune Evasion, Oncogenesis

MeSH

Bacterial Infections, Borrelia burgdorferi, Epithelial Cells, Epithelial-Mesenchymal Transition, Immune Evasion, Carcinogenesis

LCSH

Bacterial diseases, Borrelia burgdorferi, Epithelial cells, Cancer cells--Proliferation, Carcinogenesis

Abstract

Chronic bacterial infections are increasingly implicated in malignant transformation, yet the long-term cellular effects of Borrelia burgdorferi, the Lyme disease pathogen, on non-cancerous human epithelial cells remain poorly defined. This study examined how persistent B. burgdorferi exposure alters the phenotype of MCF 10A normal mammary epithelial cells using a long-term infection model. Cells were weekly infected over a 36-week period and assessed at weeks 18 and 36 for changes in morphology, proliferation, migration, invasion, epithelial–mesenchymal transition (EMT) marker expression, stemness-associated gene expression, and chromosomal karyotype alterations. Prolonged infection induced a progressive EMT shift, with infected cells acquiring elongated, spindle-like morphology accompanied by significantly increased proliferation. Functional assays revealed enhanced migratory and invasive capacity, with Matrigel invasion emerging by week 18 and further enhancing by week 36. Molecular analysis showed minimal alterations in stemness markers (CD24, CD44, ALDH1) at week 18, but strong upregulation by week 36, consistent with advanced EMT activation. This was supported by increased expression of EMT drivers, including Snail, Zeb1, N-cadherin, Vimentin, and Fibronectin. Infection also modulated inflammatory signaling. Although B. burgdorferi remained viable throughout the study (evidenced by 16S rRNA expression), CXCL10, typically elevated during acute infection, was progressively suppressed at later time points, suggesting adaptive immune evasion. Cytogenetic analysis revealed that uninfected cultures contained heterogeneous chromosomal abnormalities across multiple subclones, whereas long-term infected cultures displayed a single dominant abnormal clone, indicating infection-associated clonal selection and genomic instability. Collectively, these findings demonstrate that persistent B. burgdorferi infection drives coordinated alterations in cellular behavior, gene expression, immune signaling, and karyotypic stability, promoting a preneoplastic phenotype in non-malignant breast epithelial cells. This work provides new insight into the potential role of chronic B. burgdorferi persistence in epithelial plasticity and early oncogenic processes.

Download

Available for download on Wednesday, January 08, 2031

Off campus users: To download campus access theses or dissertations, log in to proxy server.

Share

COinS