Metronidazole-resistant strains of Trichomonas vaginalis display increasedsusceptibility to oxygen

Susceptibility to oxygen and properties relative to oxygen metabolism were compared in metronidazole-resistant and susceptible strains of Trichomonas vaginalis. The study involved clinical isolates displaying the aerobic type of resistance, as well as resistant strains developed in vitro, both with aerobic (MR-3) and anaerobic (MR-5, MR-100) resistance. Elevated sensitivit y to oxygen of the resistant clinical isolates was observed. Progressive in crease of susceptibility to oxygen also accompanied in vitro development of resistance. No correlation was found between the activity of NADH oxidase and aerobic resistance, while the in vitro derivative with fully developed anaerobic resistance (MR-100) showed about 50 % decrease of NADH oxidase ac tivity. The superoxide dismutase (SOD) activity was elevated in both resist ant clinical isolates and in in vitro-developed resistant strains. The chan ges in levels of ferredoxin were insufficient to support ferredoxin deficie ncy as a cause of aerobic metronidazole resistance. Western blot analysis a nd electron paramagnetic resonance spectroscopy of purified hydrogenosomes showed that ferredoxin is expressed in aerobically resistant strains and ha s intact iron-sulfur clusters. Down-regulation of ferredoxin was demonstrat ed only in the late phase of development of the anaerobic resistance (MR-10 0). The results support a link between aerobic resistance and defective oxy gen scavenging. The increased levels of intracellular oxygen, beneficial to resistant parasites when they interact with the drug, may have adverse eff ects on their fitness as shown by their increased sensitivity to oxidative stress.