Journal article

Delayed death in the malaria parasite Plasmodium falciparum is caused by disruption of prenylation-dependent intracellular trafficking

Kit Kennedy, Simon A Cobbold, Eric Hanssen, Jakob Birnbaum, Natalie J Spillman, Emma McHugh, Hannah Brown, Leann Tilley, Tobias Spielmann, Malcolm J McConville, Stuart A Ralph

PLOS BIOLOGY | PUBLIC LIBRARY SCIENCE | Published : 2019

Abstract

Apicomplexan parasites possess a plastid organelle called the apicoplast. Inhibitors that selectively target apicoplast housekeeping functions, including DNA replication and protein translation, are lethal for the parasite, and several (doxycycline, clindamycin, and azithromycin) are in clinical use as antimalarials. A major limitation of such drugs is that treated parasites only arrest one intraerythrocytic development cycle (approximately 48 hours) after treatment commences, a phenotype known as the ‘delayed death’ effect. The molecular basis of delayed death is a long-standing mystery in parasitology, and establishing the mechanism would aid rational clinical implementation of apicoplast-..

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