Metabolic Dysregulation Induced in Plasmodium falciparum by Dihydroartemisinin and Other Front-Line Antimalarial Drugs
Simon A Cobbold, Hwa H Chua, Brunda Nijagal, Darren J Creek, Stuart A Ralph, Malcolm J McConville
JOURNAL OF INFECTIOUS DISEASES | OXFORD UNIV PRESS INC | Published : 2016
Detailed information on the mode of action of antimalarial drugs can be used to improve existing drugs, identify new drug targets, and understand the basis of drug resistance. In this study we describe the use of a time-resolved, mass spectrometry (MS)-based metabolite profiling approach to map the metabolic perturbations induced by a panel of clinical antimalarial drugs and inhibitors on Plasmodium falciparum asexual blood stages. Drug-induced changes in metabolite levels in P. falciparum-infected erythrocytes were monitored over time using gas chromatography-MS and liquid chromatography-MS and changes in specific metabolic fluxes confirmed by nonstationary [(13)C]-glucose labeling. Dihydro..View full abstract
Awarded by Australian National Health and Medical Research Council
Awarded by R. D. Wright Biomedical Fellowship
Awarded by C. J. Martin training fellowship
This work was supported by the Australian National Health and Medical Research Council (project grant APP64095), R. D. Wright Biomedical Fellowship 1062504 to S. A. R., C. J. Martin training fellowship 628899 to D. J. C., and a NHMRC Principal Research Fellowship to M. J. M.).