Metabolic differences between metronidazole resistant and susceptible strains of Tritrichomonas foetus.
Tritrichomonas foetus mutants resistant to metronidazole lack the hydrogenosomal enzymes pyruvate: ferredoxin oxidoreductase and hydrogenase. Hydrogenosomes of these organisms did not oxidize pyruvate or produce ATP in its presence. Elimination of hydrogenosomal metabolism of pyruvate was compensated by an increased rate of glycolysis. The resistant mutants excreted no organic acids and H2 as metabolic end products. Glycolysis of the resistant T. foetus KV1-1MR-100 can be summarized as 1 mol glucose----2 mol ethanol + 2 mol CO2. The parent strain KV1, excreting H2, CO2 and acidic end products, converted about 10% of glucose to ethanol. Both strains produced ethanol from pyruvate through the action of two cytoplasmic enzymes: pyruvate decarboxylase and alcohol dehydrogenase. The specific activity of the former enzyme, catalyzing nonoxidative decarboxylation of pyruvate to acetaldehyde, was nearly seven times higher in the resistant than in the parent strain. Alcohol dehydrogenase reducing acetaldehyde to ethanol was specific to NADPH; it catalyzed the reverse reaction only slowly, and displayed similar activities in both resistant and sensitive trichomonads. Development of anaerobic metronidazole resistance in T. foetus depended on the loss of pyruvate:ferredoxin oxidoreductase as well as on the ability to increase alcoholic fermentation.
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D004352:Drug Resistance, Microbial; D005285:Fermentation; D006019:Glycolysis; D007658:Ketone Oxidoreductases / Q000378:metabolism; D008795:Metronidazole / Q000494:pharmacology*; D050743:Pyruvate Synthase; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D013045:Species Specificity; D014318:Tritrichomonas / Q000187:drug effects / Q000378:metabolism*
D011773:Pyruvates; D008795:Metronidazole; D019289:Pyruvic Acid; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D007658:Ketone Oxidoreductases; D050743:Pyruvate Synthase