Journal article

Haemoglobin degradation underpins the sensitivity of early ring stage Plasmodium falciparum to artemisinins

Stanley C Xie, Con Dogovski, Eric Hanssen, Francis Chiu, Tuo Yang, Maria P Crespo, Che Stafford, Steven Batinovic, Silvia Teguh, Susan Charman, Nectarios Klonis, Leann Tilley

JOURNAL OF CELL SCIENCE | COMPANY BIOLOGISTS LTD | Published : 2016

Abstract

Current first-line artemisinin antimalarials are threatened by the emergence of resistant Plasmodium falciparum. Decreased sensitivity is evident in the initial (early ring) stage of intraerythrocytic development, meaning that it is crucial to understand the action of artemisinins at this stage. Here, we examined the roles of iron (Fe) ions and haem in artemisinin activation in early rings using Fe ion chelators and a specific haemoglobinase inhibitor (E64d). Quantitative modelling of the antagonism accounted for its complex dependence on the chemical features of the artemisinins and on the drug exposure time, and showed that almost all artemisinin activity in early rings (>80%) is due to ha..

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