Characterizing the contribution of type IV pili and other novel virulence factors in S. sanguinis native valve infective endocarditis

Bacteria normally present in the human mouth can infect the heart valves, a disease known as infective endocarditis (IE), if they enter the bloodstream. People at risk of developing IE are those with preexisting heart conditions, artificial valves, and those that inject drugs intravenously. The presence of bacteria on the heart valve causes normal factors involved in blood clotting to form a large ‘mass’ known as a vegetation made up of these factors and the bacteria. If left untreated, this vegetation will continue to grow and prevent the heart from pumping blood efficiently, leading to heart failure. Pieces of this vegetation may also break apart and enter the bloodstream causing stroke or damage to other vital organs. Because of these issues, IE can be very serious and is associated with high levels of mortality. How bacteria from the human mouth initiate and sustain this process is not well defined, and a more thorough understanding could improve treatment and prevent infection. In this work, we tested many different genes from a representative organism, Streptococcus sanguinis, for their ability to function in different stages of disease. We identified sixteen such genes that had not previously been found to function in disease processes. Using an animal model which simulates human disease, we then tested bacteria missing one of three different genes and found that all three could no longer cause disease. One of these genes, which makes long protein stalks extending outward from bacterial cells, was then tested in more detail to determine exactly how it functions and contributes to disease. Together, this work improves our understanding of how these bacteria cause disease and provide targets for future work to develop better treatments for preventing disease from starting.