B-222. Mechanism and Gene Regulation of Streptococcus mutans Involved in the Resistance to Hydrogen Peroxide and Phagocytic Killing
The ability of an infectious agent to evade phagocytosis and resist macrophage killing is critical in the inducing systemic infection such as viridians streptococci-induced infective endocarditis (IE). This study demonstrated that Streptococcus mutans, an opportunistic IE pathogen, resist phagocytic killing after antibody-mediated phagocytosis in murine macrophage RAW 264.7 cells. To explore the mechanisms and gene regulation of this resistance, a putative two-component system (TCS), ScnR/ScnK from S. mutans was investigated. Both the wild-type and mutant strains were phagocytosed by RAW 264.7 cells at a comparable rate, isogenic scnRK-null mutants exhibited impaired intracellular survival, and increased killing of mutant strains by macrophages was not due to enhanced phagocytosis. The amount of reactive oxygen species (ROS) in activated macrophages was reduced significantly after ingesting wild-type, but not scnRK-null mutant strains, suggesting that increased killing of these mutants is due to the impaired ability of S. mutans to counteract ROS. Additionally, both scnR- or scnRK-null mutants, but not scnK-null mutant, were more susceptible to hydrogen peroxide, which contributes to the oxygen-dependent bactericidal capacity of phagocytes. The known redox-related genes (ahpF, nox, tpx, gshR, gor and sodA) was either unaffected or not significantly affected by hydrogen peroxide in scnR- or scnRK-null mutants. Interestingly, scnRK expression was unaffected by hydrogen peroxide. These experimental results indicate that scnRK is important in overcoming oxidative stress in S. mutans, and resistance to phagocytic killing is at least partly attributable to inhibited intracellular ROS.