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Published on: August 7, 2019
Delayed Death by Plastid Inhibition in Apicomplexan Parasites
Kit Kennedy1, Emily M Crisafulli1, Stuart A Ralph1
1Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, 3010, Australia.
Abstract:
The discovery of a plastid in apicomplexan parasites was hoped to be a watershed moment in the treatment of parasitic diseases as it revealed drug targets that are implicitly divergent from host molecular processes. Indeed, this organelle, known as the apicoplast, has since been a productive therapeutic target for pharmaceutical interventions against infections by Plasmodium, Toxoplasma, Babesia, and Theileria. However, some inhibitors of the apicoplast are restricted in their treatment utility because of their slow-kill kinetics, and this characteristic is called the delayed death effect. Here we review the recent genetic and pharmacological experiments that interrogate the causes of delayed death and explore the foundation of this phenomenon in Plasmodium and Toxoplasma parasites.
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