DOI
https://doi.org/10.25772/B4C7-SA86
Defense Date
2021
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Chemistry
First Advisor
Heather Lucas
Abstract
Streptococcus sanguinis is an opportunistic bacterium living beneficially in the human mouth. When S. sanguinis gains access to the bloodstream, it can result in colonization on damaged tissue and generate heart valve vegetations that can develop into infective endocarditis. It has been suggested that Mn and Fe are cofactors in the pathogenic capacity of this bacterium, and that these redox active metals are imported by the metal binding lipoprotein S. sanguinis adhesin B (SsaB). The SsaB lipoprotein is an integral part of SsaACB, an ATP-binding cassette (ABC) transport system in S. sanguinis. When SsaB is deleted, the resulting strain displays decreased virulence. The principal goal of this research has been to demonstrate the importance and fundamental properties of SsaACB as a regulator of intracellular redox maintenance within S. sanguinis and to establish its role as a dual Fe/Mn importer. In doing so, we may inspire new approaches to control the virulence of S. sanguinis. As a facultative anaerobe, deriving the variations between aerobic and anaerobic intracellular redox homeostasis in S. sanguinis and the role SsaACB has allows for a potential targeted approach for future studies. Additionally, advanced studies analyzing SsaB structural changes and competitive metal binding are also underway to shed light on the biophysical properties of SsaB and the nuances of its role in metal transport and virulence in S. sanguinis. These studies provide insight into how SsaB governs S. sanguinis redox environment, bringing clarity to the molecular details of how SsaB interacts with key biometals and shedding light on its role in metal import.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-14-2021