Hydrogen peroxide contributes to the epithelial cell death induced by the oral mitis group of streptococci.
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 (H2O2) produced by S. oralis is cytotoxic to human macrophages, suggesting that streptococcus-derived H2O2 may act as a cytotoxin. Since epithelial cells provide a physical barrier against pathogenic microbes, we investigated their susceptibility to infection by H2O2-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 H2O2, inhibited S. oralis cytotoxicity, and H2O2 alone was capable of eliciting epithelial cell death. Moreover, S. oralis mutants lacking the spxB gene encoding pyruvate oxidase, which are deficient in H2O2 production, exhibited reduced cytotoxicity toward Detroit 562 epithelial cells. In addition, enzyme-linked immunosorbent assays revealed that both S. oralis and H2O2 induced interleukin-6 production in Detroit 562 epithelial cells. These results suggest that streptococcal H2O2 is cytotoxic to epithelial cells, and promotes bacterial evasion of the host defense systems in the oral cavity and upper respiratory tracts.
Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan.
Nobuo
N
Okahashi
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan.
Tomoko
T
Sumitomo
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan.
Masanobu
M
Nakata
Department of Pediatric Dentistry and Oral Health Science Center hrc8, Tokyo Dental College, Chiba, Japan.
Atsuo
A
Sakurai
Department of Oral Microbiology and Immunology, Showa University School of Dentistry, Tokyo, Japan.
Hirotaka
H
Kuwata
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan.
Shigetada
S
Kawabata
D001426:Bacterial Proteins / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D011771:Pyruvate Oxidase / Q000378:metabolism*; D013290:Streptococcal Infections / Q000201:enzymology* / Q000473:pathology; D019533:Streptococcus oralis / Q000201:enzymology*; D013298:Streptococcus sanguis / Q000201:enzymology*
D001426:Bacterial Proteins; D006861:Hydrogen Peroxide; D011771:Pyruvate Oxidase