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
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-..View full abstract
Awarded by Australian National Health and Medical Research Council
This work was funded through grants from the Australian National Health and Medical Research Council (grants 1062504, 628704) https://www.nhmrc.gov.au/.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.