Infective endocarditis (IE) is a life-threatening disease, associated with an accumulation of bacteria and host components as vegetations on the endocardial surface of the heart. Streptococcus gordonii, an initial coloniser of the oral cavity, is frequently associated with IE pathogenesis. Previous studies have indicated the capacity for S. gordonii to interact with platelets within the blood to promote vegetation formation, mediated by surface adhesins PadA and Hsa. However, few studies have explored the ability of this bacterium to survive upon entry into the blood stream or to interact with cardiac tissue. The aim of this project was therefore to better characterise the interactions of S. gordonii with blood components and human coronary artery endothelial cells (HCAEC), with a particular focus on the roles of PadA and Hsa. Proteomic studies were used to identify interactions of PadA/Hsa with HCAEC and plasma proteins, combined with in vitro assays to investigate survival of wild-type S. gordonii or PadA/Hsa knockout mutants in human serum and their interactions with vitronectin and neutrophils. Potential strategies were identified that may enable S. gordonii to evade complement-mediated killing and other immune defences, to which both Hsa and PadA contributed. Further insight into the capacity for S. gordonii to target damaged cardiac tissue and exacerbate vegetation formation was also provided. Taken together, this information advances understanding of the mechanisms that may enable S. gordonii to survive within blood and promote IE which, in turn, could assist the development of novel treatment approaches to combat IE.
|Date of Award||26 Nov 2020|
- The University of Bristol
|Supervisor||Ruth C Massey (Supervisor) & Angela H Nobbs (Supervisor)|