title: Role of sulfhydryl compounds in the bactericidal effect of metronidazole.
abstract: The bactericidal effect of metronidazole on Escherichia coli and Bacteroides fragilis can be partially reversed by cysteamine under conditions that lead to the formation of an adduct, the thioether, 4-(2-aminoethyl)thio-2-methylimidazole-1-ethanol (4-ATME). This adduct, which is not mutagenic for the Ames histidine auxotrophs of Salmonella typhimurium, forms at a rate that is independent of live bacterial cells and, therefore, can not be shown to relate to the biological effect of cysteamine. When treated with Raney nickel, this adduct yields 2-methylimidazole-1-ethanol. To determine whether a structurally related adduct forms with bacterial protein, a culture of B. fragilis was incubated with radiolabelled metronidazole and then treated with 5% trichloroacetic acid. That the radiolabel in the precipitate did not yield 2-methylimidazole-1-ethanol when treated with Raney nickel suggests that binding of metronidazole to cellular macromolecules does not involve thioether formation.
mesh_terms: D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D001441:Bacteroides fragilis / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003543:Cysteamine / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D007093:Imidazoles / Q000378:metabolism; D008795:Metronidazole / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009152:Mutagenicity Tests; D011485:Protein Binding; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D013438:Sulfhydryl Compounds; D008795:Metronidazole; D003543:Cysteamine; C039487:4-(2-aminoethyl)thio-2-methylimidazole-1-ethanol