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Antimicrobial Agents and Chemotherapy, June 2004, p. 2185-2189, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2185-2189.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Pyruvate Decarboxylase, the Target for Omeprazole in Metronidazole-Resistant and Iron-Restricted Tritrichomonas foetus

Róbert Sutak, Jan Tachezy, Jaroslav Kulda, and Ivan Hrd^*

Department of Parasitology, Charles University, Prague, Czech Republic

Received 1 August 2003/ Returned for modification 12 November 2003/ Accepted 10 February 2004

The substituted benzimidazole omeprazole, used for the treatment of human peptic ulcer disease, inhibits the growth of the metronidazole-resistant bovine pathogen Tritrichomonas foetus in vitro (MIC at which the growth of parasite cultures is inhibited by 50%, 22 µg/ml [63 µM]). The antitrichomonad activity appears to be due to the inhibition of pyruvate decarboxylase (PDC), which is the key enzyme responsible for ethanol production and which is strongly upregulated in metronidazole-resistant trichomonads. PDC was purified to homogeneity from the cytosol of metronidazole-resistant strain. The tetrameric enzyme of 60-kDa subunits is inhibited by omeprazole (50% inhibitory concentration, 16 µg/ml). Metronidazole-susceptible T. foetus, which expresses very little PDC, is only slightly affected. Omeprazole has the same inhibitory effect on T. foetus cells grown under iron-limited conditions. Similarly to metronidazole-resistant cells, T. foetus cells grown under iron-limited conditions have nonfunctional hydrogenosomal metabolism and rely on cytosolic PDC-mediated ethanol fermentation.

This article has been cited by other articles:

• Sutak, R., Chamot, C., Tachezy, J., Camadro, J.-M., Lesuisse, E. (2004). Siderophore and haem iron use by Tritrichomonas foetus. Microbiology 150: 3979-3987 [Abstract] [Full Text]