Contribution of Streptococcus mutans Strains with Collagen-Binding Proteins in the Presence of Serum to the Pathogenesis of Infective Endocarditis.

Abstract

Streptococcus mutans, a major pathogen of dental caries, is considered one of the causative agents of infective endocarditis (IE). Recently, bacterial DNA encoding 120-kDa cell surface collagen-binding proteins (CBPs) has frequently been detected from S. mutans-positive IE patients. In addition, some of the CBP-positive S. mutans strains lacked a 190-kDa protein antigen (PA), whose absence strengthened the adhesion to and invasion of endothelial cells. The interaction between pathogenic bacteria and serum or plasma is considered an important virulence factor in developing systemic diseases; thus, we decided to analyze the pathogenesis of IE induced by S. mutans strains with different patterns of CBP and PA expression by focusing on the interaction with serum or plasma. CBP-positive (CBP+)/PA-negative (PA-) strains showed prominent aggregation in the presence of human serum or plasma, which was significantly greater than that with CBP+/PA-positive (PA+) and CBP-negative (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. In addition, aggregation of CBP+/PA- strains was drastically reduced when serum complement was inactivated. Furthermore, an ex vivo adherence model and an in vivo rat model of IE showed that extirpated heart valves infected with CBP+/PA- strains displayed prominent bacterial mass formation, which was not observed following infection with CBP+/PA+ and CBP-/PA+ strains. These results suggest that CBP+/PA-S. mutans strains utilize serum to contribute to their pathogenicity in IE.