Adhesins of Streptococcus sanguinis that promote infective endocarditis through interactions with platelets

Infective endocarditis (IE) is a bacterial infection of the heart. For IE to occur the heart valve must be injured or inflamed, which can arise from congenital heart disease, rheumatic heart disease, intravenous drug use, or the presence of an artificial valve. Bacteria can stick to multiple factors at the site of injury and grow into biofilm-like masses called vegetations. These vegetations can impair heart function and break off, causing blood clots (emboli) throughout the body. IE is associated with a high mortality rate even with treatment. How bacteria cause this disease is relatively unknown and understudied. We set out to look for factors that the bacterium, Streptococcus sanguinis, use to cause IE. We created mutant strains in sixteen different genes that were unable to function in various tests that mimic IE progression. Three of these factors were tested in an animal model and found to be unable to cause disease. We characterized two of these factors in more detail. The first factor, PbrA, is a unique protein that cleaves itself, is surface associated, and interacts with platelets. The other factor is a type IV pili (T4P) system, which is composed of small proteins that are extended out of the bacteria and can be retracted back and one of its functions is to mediate twitching motility. We found that T4P are needed to produce a platelet-dependent biofilm as well as invade aortic endothelial cells. Together this work improves our understanding on how S. sanguinis causes IE and provides foundations for future research in the development of preventatives and treatments.