Inactivation of Clostridium difficile cytotoxin by the neutrophil myeloperoxidase system.
The cytotoxin of Clostridium difficile was examined for sensitivity to oxidant secretory products of neutrophils. Exposure to myeloperoxidase, H2O2, and a halide resulted in loss of toxin activity measured by tissue-culture cytotoxicity. The peroxide requirement was provided by reagent H2O2, a peroxide-generating enzyme (glucose oxidase), or a peroxide-producing intestinal microorganism, Lactobacillus acidophilus. Human neutrophils stimulated by phorbol myristate acetate caused similar toxin inactivation. In both the cell-free and the neutrophil systems, inactivation of toxin required halides and was abrogated by azide, cyanide, or catalase. Neutrophils from patients with lack of myeloperoxidase or failure to produce H2O2 were impaired in toxin inactivation unless myeloperoxidase or H2O2, respectively, was added. The reducing agent 2-mercaptoethanol enhanced toxin activity. These data suggest a similarity between C difficile cytotoxin and the classic thiol-activated cytolysins. Moreover, they raise the possibility that neutrophils are involved in oxidative detoxification of microbial products.
D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D003015:Clostridium Infections / Q000276:immunology; D003603:Cytotoxins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004761:Enterocolitis, Pseudomembranous / Q000276:immunology / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005947:Glucose / Q000378:metabolism; D005949:Glucose Oxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007454:Iodides / Q000378:metabolism; D007779:Lactobacillus acidophilus / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D002712:Chlorides; D003603:Cytotoxins; D007454:Iodides; C031815:toxB protein, Clostridium difficile; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D010544:Peroxidases; D009195:Peroxidase; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate