title: Inhibition of Clostridium difficile toxin A and B by 1,2-cyclohexanedione modification of an arginine residue.
abstract: Toxin A (enterotoxin) and toxin B (cytotoxin) of Clostridium difficile were both inactivated by the arginine specific reagent 1,2-cyclohexanedione. Molecular stability during the inactivation process was demonstrated by SDS-PAGE analysis showing the same migration rates for modified and unmodified forms of the 230 kDa toxin A and of the 250 kDa toxin B. Cytotoxicity of both toxins as well as mouse lethality of the enterotoxin were drastically decreased as a result of the arginine modification. The reaction followed pseudo-first-order kinetics. Analysis of the data suggested that modification of a single arginine residue was sufficient to abolish the activity of both toxins.
authors.affiliation: Dept. of Medical Microbiology, University of Kiel, FRG.
authors.forename: J
authors.initials: J
authors.lastname: Balfanz
authors.forename: P
authors.initials: P
authors.lastname: Rautenberg
mesh_terms: D000818:Animals; D001120:Arginine; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000633:toxicity; D002470:Cell Survival; D003013:Clostridium; D003510:Cyclohexanes / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004768:Enterotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000633:toxicity; D007700:Kinetics; D007928:Lethal Dose 50; D051379:Mice; D008809:Mice, Inbred C3H; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003510:Cyclohexanes; D003512:Cyclohexanones; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; C018031:1,2-cyclohexanedione; D001120:Arginine