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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Grants

Awarded by Australian National Health and Medical Research Council


Funding Acknowledgements

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.