Role of sulfhydryl compounds in the bactericidal effect of metronidazole.
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.
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*
D007093:Imidazoles; D013438:Sulfhydryl Compounds; D008795:Metronidazole; D003543:Cysteamine; C039487:4-(2-aminoethyl)thio-2-methylimidazole-1-ethanol