The effects of ponazuril on development of apicomplexans in vitro.

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Mitchell SM, Zajac AM, Davis WL, Kennedy TJ, Lindsay DS

The effects of ponazuril on development of apicomplexans in vitro.

J Eukaryot Microbiol. 2005 May-Jun;52(3):231-5.

PubMed ID
15926999 [ View in PubMed
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Abstract

We examined the effects of 5 microg/ml ponazuril treatment on developing tachyzoites of Neospora caninum and merozoites of Sarcocystis neurona to better determine the mode of action of this anticoccidial drug. Both parasites develop asexually by endogenesis. Neospora caninum was selected for study because it develops by endodyogeny, which results in two tachyzoites being produced internally, and S. neurona was selected because it develops by endopolygeny which results in many merozoites being produced internally. Ponazuril inhibited development of N. caninum after approximately 48 h post-exposure. Treated tachyzoites of N. caninum developed vacuoles and underwent degeneration. Ponazuril also inhibited development of merozoites of S. neurona. Treated merozoites and maturing schizonts of S. neurona developed vacuoles and underwent degeneration. The ability of S. neurona schizonts to undergo cytokinesis was inhibited. Our results are discussed in relation to previous ultrastructural research on endogenesis of tachyzoites of Toxoplasma gondii undergoing endodyogeny which indicated that ponazuril induced multinucleate stage formation and inhibited cytokinesis. Ponazuril is believed to act on the apicoplast and our study demonstrates that this agent may express its inhibitory effects in different phenotypic manners on different apicomplexan parasites. The enzyme/enzyme systems that are the inhibitory target of ponazuril may be different in these apicomplexans, or the results of inhibition may affect different pathways downstream of its initial site of action in these parasites.

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