Ferredoxin-dependent reduction of nitroimidazole derivatives in drug-resistant and susceptible strains of Trichomonas vaginalis.
The inhibitory effect of a range of nitroimidazole-derivatives on H2 production by metronidazole resistant (CDC-85) and susceptible (C1-NIH) Trichomonas vaginalis strains was investigated. The 2-, 4-, and 5-nitro-derivatives used had one-electron reduction potentials within the range -250 to -525 mV. Nitroimidazole concentrations giving 50% inhibition of H2 production (kiH2) for compounds with one-electron reduction potentials in the range -250 to -425 mV were found to be similar for both strains tested. Compounds with one-electron reduction potentials below -425 mV give 10-fold higher KiH2 values for the metronidazole resistant isolate. Both strains showed increased KiH2 for compounds with potentials lower than -500 mV. The addition of 2.1 kPa (0.02 atm) O2 to the gas phase resulted in increasing the kiH2 values for all the compounds tested, but had the greater effect on results obtained with the resistant isolate using nitroimidazoles in the range -425 to -490 mV. The results enable the proposal that the resistant isolate CDC-85 has a ferredoxin with altered redox properties or reduced intracellular levels.
D000818:Animals; D002465:Cell Movement; D004352:Drug Resistance, Microbial; D005288:Ferredoxins / Q000502:physiology*; D006859:Hydrogen / Q000378:metabolism; D007700:Kinetics; D013058:Mass Spectrometry; D009593:Nitroimidazoles / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D014246:Trichomonas vaginalis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D005288:Ferredoxins; D009593:Nitroimidazoles; D006859:Hydrogen; D010100:Oxygen