Metabolomics

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Piperaquine-resistant PfCRT mutations differentially impact drug transport, hemoglobin catabolism and parasite physiology in Plasmodium falciparum asexual blood stages.


ABSTRACT: The emergence of multidrug resistance in Plasmodium falciparum parasites presents a significant obstacle to the malaria elimination agenda. Resistance to piperaquine (PPQ), an important first-line partner drug, has spread across Southeast Asia where it has contributed to widespread treatment failures. The genetic cause of resistance to PPQ is attributable to a novel set of amino acid substitutions in the P. falciparum chloroquine resistance transporter (PfCRT). In this study, we used magnetically-purified trophozoite extracts from seven different lines comprising five genetically-modified and two field isolates. Three independent extractions with triplicate technical repeats were run by mass spectrometry on positive and negative modes and spectral peak raw data analyzed to obtain the fold change difference between the samples and parental control, Dd2Dd2crt. We show that PPQ-resistant, PfCRT mutant asexual blood stage parasites accumulate higher levels of hemoglobin-derived peptides than do their PPQ-sensitive counterparts.

ORGANISM(S): Plasmodium Falciparum

TISSUE(S): Cultured Cells

DISEASE(S): Malaria

SUBMITTER: Manuel Llinas  

PROVIDER: ST002181 | MetabolomicsWorkbench | Wed May 18 00:00:00 BST 2022

REPOSITORIES: MetabolomicsWorkbench

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