Altered Drug Transport by Plasmodium Falciparum Chloroquine Resistance Transporter Isoforms Harboring Mutations Associated with Piperaquine Resistance.

Patterns of multiple amino acid substitutions in the Plasmodium falciparum chloroquine resistance transporter (PfCRT; UniProtKB - Q8IBZ9) have previously been shown to mediate chloroquine resistance (CQR) in P. falciparum malarial parasites. Recent reports suggest that novel mutations in PfCRT may mediate resistance to piperaquine (PPQ), which is used extensively as a partner drug in one prominent artemisinin combination therapy (ACT). How these novel PfCRT isoforms might mediate PPQ resistance (PPQR) is not known. Using codon optimization and other previously perfected methods for PfCRT analysis in yeast, we have expressed all known PPQR - associated PfCRT isoforms in S. cerevisiae yeast and have tested whether these isoforms catalyze PPQ transport. Relationships between relative PPQ vs CQ transport are analyzed for these isoforms vs other previously recognized drug resistance - associated PfCRT isoforms.

• Publication year

  2020

• Venue

  Biochemistry

• Publication date

  2020-06-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1021/acs.biochem.0c00247PMID 32589406
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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