Author ORCID Identifier
https://orcid.org/0009-0001-2375-496X
Defense Date
2024
Document Type
Thesis
Degree Name
Master of Science
Department
Microbiology & Immunology
First Advisor
Todd Kitten
Second Advisor
Kimberly Jefferson
Third Advisor
Martin Mangino
Fourth Advisor
Rebecca Martin
Abstract
Infective endocarditis (IE) is a rare, life-threatening disease caused by infection of the endocardium of the heart. It is characterized by the development of vegetations on heart valves that consist of bacteria embedded within a matrix of platelets and fibrin. Streptococcus sanguinis is an oral commensal that can cause IE if it enters the bloodstream in persons with cardiac conditions that promote the formation of sterile vegetations. A previous study employing an in vivo animal model of IE compared multiple strains of S. sanguinis and revealed large differences in the number of bacteria recovered from vegetations for strains SK405, SK36, and SK115, with SK405 recovered in the highest numbers and SK115 the lowest. Platelets play a central and dual role in the development of IE. They adhere to damaged heart valves to promote wound healing, but also serve as an attachment site for S. sanguinis to infect the endocardium. Previous studies have demonstrated the role platelets serve in host defense by secreting antimicrobials and recruiting other immune cells to protect against endovascular infection. The structure of vegetations places S. sanguinis in close proximity to platelets, where the bacteria may be exposed to platelet antimicrobial proteins. As such, resistance to platelet antimicrobial proteins may be necessary to establish an infection and susceptibility to platelet-mediated killing could explain our in vivo results. In the present study, an ex vivo assay was developed to assess the sensitivity of S. sanguinis strains SK405, SK36 and SK115 to inhibition by rabbit platelets. Whole blood was collected from New Zealand White rabbits into standard sodium citrate tubes and centrifuged to collect platelet-rich plasma and platelet-poor plasma. S. sanguinis strains were incubated with platelets that were stimulated with either a variety of platelet agonists or no agonist for varying lengths of time. Agonist-stimulated platelets formed clots. Although the clots occupied much less volume than the remaining serum, virtually all of the bacterial cells of all three strains were found within the clots. The number of bacterial cells recovered from stimulated platelets was generally indistinguishable for the three strains, even when longer incubation times or different platelet agonists were tested. The results suggest that differential binding to platelets or sensitivity to platelet antimicrobial proteins is unlikely to be responsible for the differences among these strains observed in the animal model.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
4-29-2024
Included in
Bacteria Commons, Bacterial Infections and Mycoses Commons, Bacteriology Commons, Cardiovascular Diseases Commons, Immunology of Infectious Disease Commons, Oral Biology and Oral Pathology Commons