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Comparative in vitro evaluation of the activity of proton pump inhibitor compounds against a bovine-derived Tritrichomonas foetus strain
Ungvárszky Martin Alex - year 5
University of Veterinary Medicine Budapest, Department of Pharmacology and Toxicology
Supervisors: Dr. Ádám Kerek, Dr. Melinda Nemes-Terényi

Abstract:

Bovine trichomonosis caused by Tritrichomonas foetus is an important reproductive disease, particularly in cattle populations relying on natural breeding. Infected bulls may become persistent, largely asymptomatic carriers, whereas females may develop early embryonic loss, repeat breeding, infertility or abortion. Therapeutic options are limited because 5-nitroimidazoles, despite their antitrichomonal activity, are not suitable for use in food-producing cattle. We therefore compared the in vitro activity of five repurposable proton pump inhibitors (PPIs)—pantoprazole, omeprazole, esomeprazole, lansoprazole and rabeprazole—against the bovine T. foetus reference strain ATCC 30232.

The parasite was maintained in CPLM-based medium supplemented with heat-inactivated horse serum at 37 °C under 5% CO₂. Compounds were tested for 24 h in two-fold dilution series ranging from 4000 to 1.953 µg/mL. Motile trophozoites were quantified using a Bürker chamber, with five large counting squares assessed per condition. Concentration-matched ethanol controls were included for omeprazole, esomeprazole and lansoprazole. Concentration–response trends were evaluated using Spearman rank correlations with Benjamini–Hochberg correction.

The lowest concentrations at which no motile trophozoites were detected were 31.25 µg/mL for lansoprazole, 250 µg/mL for omeprazole, and 500 µg/mL for pantoprazole, esomeprazole and rabeprazole. Pantoprazole yielded the same 500 µg/mL threshold in two separate experimental runs, with strong agreement between normalized profiles (ρ=0.801, p=0.0017). Spearman trend analyses yielded BH-adjusted q values ≤0.0104 for all five PPIs. Lansoprazole produced 94.1% vehicle-corrected inhibition at 15.625 µg/mL and 76.2% at 7.8125 µg/mL, while the activity of omeprazole at 250 µg/mL was also clearly distinguishable from ethanol toxicity.

Compared with our previously published Trichomonas gallinae dataset, the bovine strain showed substantially lower inhibition thresholds for lansoprazole, rabeprazole, pantoprazole and esomeprazole, whereas omeprazole remained unchanged, suggesting species- and strain-dependent pharmacological responses. Because T. foetus can form drug-tolerant cysts, loss of motility should not be interpreted as irreversible parasite death. Lansoprazole, omeprazole and pantoprazole therefore emerge as the most promising candidates for further validation using multiple bovine isolates, independent biological replicates, recovery assays and complementary viability endpoints.



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