title: Hydrogen peroxide produced by oral Streptococci induces macrophage cell death.
abstract: Hydrogen peroxide (H2O2) produced by members of the mitis group of oral streptococci plays important roles in microbial communities such as oral biofilms. Although the cytotoxicity of H2O2 has been widely recognized, the effects of H2O2 produced by oral streptococci on host defense systems remain unknown. In the present study, we investigated the effect of H2O2 produced by Streptococcus oralis on human macrophage cell death. Infection by S. oralis was found to stimulate cell death of a THP-1 human macrophage cell line at multiplicities of infection greater than 100. Catalase, an enzyme that catalyzes the decomposition of H2O2, inhibited the cytotoxic effect of S. oralis. S. oralis deletion mutants lacking the spxB gene, which encodes pyruvate oxidase, and are therefore deficient in H2O2 production, showed reduced cytotoxicity toward THP-1 macrophages. Furthermore, H2O2 alone was capable of inducing cell death. The cytotoxic effect seemed to be independent of inflammatory responses, because H2O2 was not a potent stimulator of tumor necrosis factor-α production in macrophages. These results indicate that streptococcal H2O2 plays a role as a cytotoxin, and is implicated in the cell death of infected human macrophages.
authors: Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan. okahashi@dent.osaka-u.ac.jp
authors: Nobuo
authors: N
authors: Okahashi
authors: Masanobu
authors: M
authors: Nakata
authors: Tomoko
authors: T
authors: Sumitomo
authors: Yutaka
authors: Y
authors: Terao
authors: Shigetada
authors: S
authors: Kawabata
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003603:Cytotoxins / Q000096:biosynthesis / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D011771:Pyruvate Oxidase / Q000172:deficiency / Q000235:genetics; D019533:Streptococcus oralis / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; D003603:Cytotoxins; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D002374:Catalase; D011771:Pyruvate Oxidase
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