Thesis Format
Monograph
Degree
Master of Science
Program
Microbiology and Immunology
Supervisor
Heinrichs, David
Abstract
Staphylococcus aureus infection relies on a large array of virulence factors, such as fibronectin-binding protein A (FnBP-A). Previously shown by our lab, inactivation of the purine biosynthesis repressor (PurR) aberrantly upregulates FnBP-A, which underpins hyper-clumping in serum. Furthermore, preliminary data generated by our lab revealed that deletion of either SaeRS or ArlRS abolishes PurR-dependent hyper-clumping. Thus, I hypothesize that PurR, SaeRS and ArlRS coordinately regulate FnBP-A. I performed clumping assays to show that complementation of saeRS and arlRS restored the hyper-clumping phenotype in the aforementioned double mutants. Furthermore, inactivation of saeRS or arlRS in a purR mutant, reduced fnbA transcript level and FnBP-A expression. I overexpressed and purified SaeS, SaeR and PurR proteins, and subsequently performed electrophoretic mobility shift assays to show that PurR and SaeR directly bind to the fnbA promoter/operator region, suggesting that SaeR and PurR regulate FnBP-A expression by modulating fnbA transcription.
Summary for Lay Audience
Staphylococcus aureus (S. aureus) is a common pathogen responsible for causing minor skin infections as well as life-threatening diseases. One key factor that is responsible for the severity of S. aureus infection is its ability to express a wide array of proteins to help it colonize or damage host tissues. Fibronectin-binding protein A (FnBP-A) is a protein that locates at the S. aureus surface and helps the bacteria stick to the host, establishing bacterial colonization. Here, I studied the regulation of FnBP-A by multiple regulators in different growth phases. Overall, this study contributes to our understanding of how S. aureus regulates proteins that are involved in virulence, providing more insight into developing new therapies.
Recommended Citation
Zhang, Yunqi, "Investigating the role of two-component regulatory systems in regulating FnBP-A of Staphylococcus aureus" (2024). Electronic Thesis and Dissertation Repository. 9930.
https://ir.lib.uwo.ca/etd/9930