Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Antimicrob Agents Chemother. 2010 May;54(5):1872-7. doi: 10.1128/AAC.01636-09. Epub 2010 Feb 16.

Increased tolerance to artemisinin in Plasmodium falciparum is mediated by a quiescence mechanism.

Author information

  • 1CNRS, Laboratoire de Chimie de Coordination, UPR8241, Toulouse, France.

Abstract

Artemisinin (ART)-based combination therapies (ACTs) are the first-line drugs-and often the last treatments-that can effectively cure Plasmodium falciparum infections. Unfortunately, the decreased clinical efficacy of artesunate, one of the major ART derivatives, was recently reported along the Thailand-Cambodia border. Through long-term artemisinin pressure in vitro, we have obtained an ART-tolerant strain that can survive extremely high doses of ART. We showed that drug pressure could induce a subpopulation of ring stages into developmental arrest, which can explain the ART tolerance in P. falciparum. We also observed interesting transcriptomic modifications possibly associated with the acquisition of ART tolerance. These modifications include the overexpression of heat shock and erythrocyte surface proteins and the downexpression of a cell cycle regulator and a DNA biosynthesis protein. This study highlights a new phenomenon in the Plasmodium response to ART that may explain the delayed clearance of parasites after artesunate treatment observed on the Thailand-Cambodia border and that provides important information for achieving a better understanding of the mechanisms of antimalarial resistance.

PMID:
20160056
[PubMed - indexed for MEDLINE]
PMCID:
PMC2863624
Free PMC Article

Images from this publication.See all images (3)Free text

FIG. 1.
FIG. 2.
FIG. 3.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk