title: Metronidazole uptake in Helicobacter pylori.
abstract: Currently, the mechanism of metronidazole resistance is not understood in Helicobacter pylori. We have looked at uptake of metronidazole into a sensitive and a resistant strain of H. pylori. Both strains displayed rapid uptake of [14C]metronidazole, although the resistant strain accumulated the drug at a slower rate and to a lesser amount than the sensitive strain. Uptake was inhibited by KCN and carbonyl cyanide m-chlorophenyl-hydrazone (CCCP) but not by sodium arsenate. Thin-layer chromatography analysis of lysed cell supernatants showed that metronidazole was metabolized in both strains. A variety of related imidazole compounds inhibited metronidazole uptake, consistent with a common transport system for this group of antibiotics. Our data do not support an absence of uptake or metabolism as a cause of resistance in the strain examined.
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Moore
authors.forename: B
authors.initials: B
authors.lastname: Beckthold
authors.forename: L E
authors.initials: LE
authors.lastname: Bryan
mesh_terms: D001693:Biological Transport, Active / Q000187:drug effects; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D016481:Helicobacter Infections / Q000188:drug therapy; D016480:Helicobacter pylori / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D008795:Metronidazole / Q000493:pharmacokinetics* / Q000494:pharmacology; D011190:Potassium Cyanide / Q000494:pharmacology
chemical_list: D007093:Imidazoles; D008795:Metronidazole; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D011190:Potassium Cyanide