Journal article

K13, the Cytostome, and Artemisinin Resistance

Stanley C Xie, Stuart A Ralph, Leann Tilley

Trends in Parasitology | ELSEVIER SCI LTD | Published : 2020

Abstract

Artemisinins - the frontline antimalarial drug class - are compromised by emerging resistance, putting at risk the lives of hundreds of thousands of people each year. Resistance is associated with mutations in a malaria parasite protein, called Kelch 13 (K13). Recent work suggests that K13 is located at the cytostome (cell mouth) that the parasite uses to take up hemoglobin. Here we explore the proposal that K13 mutations confer artemisinin resistance by dampening hemoglobin endocytosis. This model suggests that the resultant decrease in hemoglobin-derived heme reduces artemisinin activation, which is sufficient to enable parasite survival in the early ring stage of infection. A fuller under..

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Grants

Funding Acknowledgements

This work was supported by the National Health & Medical Research Council of Australia (NHMRC) and the Australian Research Council (ARC). We thank Madel Tutor, Eric Hanssen, and Paul McMillan, University of Melbourne, for assistance with preparation of micrograph images.