title: The effects of ponazuril on development of apicomplexans in vitro.
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.
authors.affiliation: Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0342, USA.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Mitchell
authors.forename: Anne M
authors.initials: AM
authors.lastname: Zajac
authors.forename: Wendell L
authors.initials: WL
authors.lastname: Davis
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kennedy
authors.forename: David S
authors.initials: DS
authors.lastname: Lindsay
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D048749:Cytokinesis / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects; D018688:Neospora / Q000187:drug effects* / Q000648:ultrastructure; D012522:Sarcocystis / Q000187:drug effects* / Q000648:ultrastructure; D014122:Toxoplasma; D014227:Triazines / Q000494:pharmacology*; D014617:Vacuoles
chemical_list: D000981:Antiprotozoal Agents; D014227:Triazines; C415002:ponazuril