For example, this approach demonstrated pilus involvement in attachment to collagen by Streptococcus gallolyticus. This was the first time that a virulence factor was demonstrated in an animal model of Interestingly, strains that expressed pil1 did not adhere to either fibronectin or fibrinogen but did form biofilm in vitro. A nonpathological Lactococcus lactis strain that by recombinant techniques expressed Pil1 in vitro was examined with its parent strain that did not express Pil1 in a rat model of experimental endocarditis. The results suggested that Pil1 was important in vivo as a virulence factor; 82% of rats challenged with the Pil1+ strain developed experimental endocarditis, in contrast to the animals that received the Pil1 strain (36%, The big 3 pathogens (viridans group streptococci [VGS], S aureus, and Enterococcus species) that account for the large majority of endocarditis cases have been the primary focus of pathogenesis studies.31 Adhesins of S aureus, which have been referred to as MSCRAMMs (microbial surface com- ponents recognizing adhesive matrix molecules), are surface molecules involved in staphylococcal attachment to collagen, thrombospondin, laminin, fibrinogen, and fibronectin.32 These interactions with host proteins not only may be important in the initial adherence of bacteria to a site of endothelial damage but also may be operative in bacterial persistence and engulf- ment by the host cell (endothelial cells, platelets). Similarly, there have been several bacterial surface structures identified in strains of VGS and Enterococcus species that appear criti- cal in endocarditis pathogenesis. Study of pathogenic mechanisms in IE is pivotal as we consider potential advances in infection treatment and preven- tion in the future. This knowledge serves as a foundation for the development of novel clinical tools that include therapeu- tics and vaccines. 