Advisory Committee Chair
Palaniappan Sethu
Advisory Committee Members
Juhi Samal
Min Xie
Document Type
Thesis
Date of Award
1-1-2025
Degree Name by School
Master of Biomedical Engineering (MBE) School of Engineering
Abstract
Streptococcus pneumoniae (Spn) is a gram-positive bacterium that causes community-acquired pneumonia, the most prevalent type of pneumonia and a predominant infectious disease. There is evidence linking Spn infection to cardiovascular damage through the ability of Spn to invade and replicate in the myocardium, inducing cardiomyocyte death and disrupting cardiac function. Spn infects cardiomyocytes intracellularly through clathrin-mediated endocytosis, with demonstrated evidence of inhibitory mechanisms including clathrin-mediated endocytosis inhibitors and antioxidants. As a result, autophagy is being investigated as a potential pathway for cardiomyocyte self-defense against Spn, as it may protect cardiomyocytes intracellularly. The primary objective of this study was to evaluate methods for characterizing the role of autophagy in cardiomyocyte protection following Spn infection in vitro in two- and three-dimensional cell architecture. Experiments utilized normal human-induced pluripotent stem cell-derived cardiomyocytes treated with an autophagy inhibitor and promoter, Bafilomycin A and Tat-Beclin1, respectively. Analyses of bacterial mNeonGreen fluorescence, lactate dehydrogenase, and cytokine results concluded that autophagy promotion leads to lower cell cytotoxicity and bacterial infection compared to autophagy inhibition in Spn infected cells. A primary advantage of three-dimensional cell architecture was its ability to form bacterium-filled microlesions characteristic of Spn infection in the heart, rendering it superior to two-dimensional. Characterization of a polydimethylsiloxane membrane cardiac tissue chip was also performed, as the cardiac tissue chip enables in vitro modulation of stretch and pressure. The study was intended to advance the understanding of cardiac response to Spn infection and lead to enhanced approaches for the study of cardiac injury.
Recommended Citation
Khong, Georgianna, "Evaluation of in vitro cardiac models for characterizing the role of autophagy in Streptococcus pneumoniae infection" (2025). All ETDs from UAB. 6857.
https://digitalcommons.library.uab.edu/etd-collection/6857
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