Contribution of Reaction of Streptococcus mutans Cell Surface Structure to Blood Components in Pathogenesis of Infective Endocarditis

Abstract

Streptococcus mutans is a major pathogen of dental caries and also considered to be one of the causative agents of infective endocarditis (IE). Recent studies have noted frequent detection of bacterial DNA encoding 120-kDa cell surface collagen-binding proteins (CBPs) in samples obtained from S. mutans-positive IE patients. In addition, some CBP-positive S. mutans strains have been found to lack the 190-kDa protein antigen (PA), and that absence strengthened bacterial adhesion to and invasion of endothelial cells. Interaction of pathogenic bacteria with serum or plasma is considered to be an important virulence factor for systemic disease development. In the present study, the pathogenesis of IE induced by S. mutans strains was examined based on different CBP and PA expression patterns,with focus on interactions with serum and plasma. CBP＋/PA－strains showed prominent aggregation in the presence of human serum or plasma, which was significantly greater than that of the examined CBP＋/PA＋and CBP－/PA＋strains. Aggregation of CBP＋/PA－strains was also observed in the presence of a high concentration of type IV collagen, a major extracellular matrix protein in serum, while that was drastically reduced when the serum complement was inactivated. Furthermore, findings from an ex vivo adherence model and in vivo rat model of IE showed that extirpated heart valves infected with CBP＋/PA－strains had prominent bacterial mass formation, which was not observed following infection with CBP＋/PA＋or CBP－/PA＋strains. These results suggest that CBP＋/PA－S. mutans strains utilize serum to contribute to the pathogenicity of IE.