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Members of the mitis group of streptococci are normal inhabitants of the commensal flora of the oral cavity and upper respiratory tract of humans. Some mitis group species, such as  Streptococcus oralis  and  Streptococcus sanguinis , are primary colonizers of the human oral cavity. Recently, we found that hydrogen peroxide (H 2 O 2 ) produced by  S. oralis  is cytotoxic to human macrophages, suggesting that streptococcus-derived H 2 O 2  may act as a cytotoxin. Since epithelial cells provide a physical barrier against pathogenic microbes, we investigated their susceptibility to infection by H 2 O 2 -producing streptococci in this study. Infection by  S. oralis  and  S. sanguinis  was found to stimulate cell death of Detroit 562, Calu-3 and HeLa epithelial cell lines at a multiplicity of infection greater than 100. Catalase, an enzyme that catalyzes the decomposition of H 2 O 2 , inhibited  S. oralis  cytotoxicity, and H 2 O 2  alone was capable of eliciting epithelial cell death. Moreover,  S. oralis  mutants lacking the  spxB  gene encoding pyruvate oxidase, which are deficient in H 2 O 2  production, exhibited reduced cytotoxicity toward Detroit 562 epithelial cells. In addition, enzyme-linked immunosorbent assays revealed that both  S. oralis  and H 2 O 2  induced interleukin-6 production in Detroit 562 epithelial cells. These results suggest that streptococcal H 2 O 2  is cytotoxic to epithelial cells, and promotes bacterial evasion of the host defense systems in the oral cavity and upper respiratory tracts.

Hydrogen Peroxide Contributes to the Epithelial Cell Death Induced by the Oral Mitis Group of Streptococci