In Vitro Killing of Babesia bovis by the Ornithine Analog α-monofluoromethyldehydroornithine Methyl Ester

The effects of the 2 ornithine decarboxylase inhibitors α-difluoromethylomithine (DFMO) and α-monofluoromethyl-dehydroormithine methyl ester (ΔMFMO-ME) on growth ofBabesia bovis blood stages in vitro were tested. The DFMO had no apparent effects on in vitro growth of B. bovis nor on the morphology of the parasite at concentrations up to 20 mM. In contrast, ΔMFMO-ME had cytotoxic effects on B. bovis at 0.5 mM which were more pronounced at 5 mM. ΔMFMO-ME caused both a decrease in percentage parasitized erythrocytes and a degeneration of parasites after 12 h exposure, and the magnitude of both effects was dose-dependent. The effects of ΔMFMO-ME were not reversible for B. bovis precultured for 12 h (5 mM) or 24 h (0.5 mM) in drug before culturing the parasite in drug-free medium. Unexpectedly, 300 μM putrescine did not reverse the effects of ΔMFMO-ME on B. bovis blood stage, raising the possibility that inhibition of omithine decarboxylase is not responsible for these effects.