Rasoloson, D., Tomková,
E., Cammack, R., Kulda, J., Tachezy, J. 2001. Metronidazole resistant strains
of Trichomonas vaginalis display increased susceptibility to oxygen. Parasitology,
123: 45-56.
Keywords
metronidazole-resistant
Trichomonas vaginalis, oxygen sensitivity, superoxide dismutase, NADH oxidase,
ferredoxin CONTAINING SUPEROXIDE-DISMUTASE, TRITRICHOMONAS-FOETUS, ENTAMOEBA-HISTOLYTICA,
ANAEROBIC RESISTANCE, CARBON-DIOXIDE, INVITRO, HYDROGENOSOMES, PURIFICATION,
METABOLISM, GROWTH
Abstract:
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 sensitivity to oxygen of the resistant
clinical isolates was observed. Progressive increase 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 activity. The superoxide dismutase (SOD) activity
was elevated in both resistant clinical isolates and in in vitro-developed resistant
strains. The changes in levels of ferredoxin were insufficient to support ferredoxin
deficiency as a cause of aerobic metronidazole resistance. Western blot analysis
and electron paramagnetic resonance spectroscopy of purified hydrogenosomes
showed that ferredoxin is expressed in aerobically resistant strains and has
intact iron-sulfur clusters. Down-regulation of ferredoxin was demonstrated
only in the late phase of development of the anaerobic resistance (MR-100).
The results support a link between aerobic resistance and defective oxygen scavenging.
The increased levels of intracellular oxygen, beneficial to resistant parasites
when they interact with the drug, may have adverse effects on their fitness
as shown by their increased sensitivity to oxidative stress.
ISSN 0031-1820
IF 1,944
UK