K13, the Cytostome, and Artemisinin Resistance.

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 understanding of the resistance mechanism will underpin efforts to develop alternative antimalarial strategies.

• Authors: Stanley C Xie, Stuart A Ralph, Leann Tilley
• Journal: Trends in parasitology (Trends Parasitol) Vol. 36 Issue 6 Pg. 533-544 (06 2020) ISSN: 1471-5007 [Electronic] England
• PMID: 32359872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Antimalarials
• Artemisinins
• Protozoan Proteins
• Heme

Topics

• Antimalarials (pharmacology)
• Artemisinins (pharmacology)
• Drug Resistance (genetics)
• Heme (metabolism)
• Humans
• Mutation
• Plasmodium (drug effects, genetics, metabolism)
• Protozoan Proteins (genetics, metabolism)