Plasmodium falciparum resistance to chloroquine, the former gold standard antimalarial drug, is mediated primarily by mutant forms of the ‘Chloroquine Resistance Transporter’ (PfCRT). These mutations impart upon PfCRT the ability to efflux chloroquine from the intracellular digestive vacuole, the site of drug action.

2005年6月1日 · A major breakthrough in the search for the genetic basis of CQR in P. falciparum was the identification of pfcrt gene, which encodes a putative transporter or channel protein (Fidock et al., 2000). PfCRT is a 48 kDa protein containing 424 amino acids, 10 predicted transmembrane-spanning domains and is localized to the DV membrane in ...

2020年3月16日 · Mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) confer resistance to several antimalarial drugs such as chloroquine (CQ) or piperaquine (PPQ),...

2016年11月30日 · The mutations in the digestive vacuole transmembrane protein Plasmodium falciparum chloroquine resistance transporter (PfCRT) are mainly responsible for chloroquine resistance (CQR) in Plasmodium falciparum. Multiple mutations in the PfCRT are concerned in chloroquine resistance, but the evolution of intricate haplotypes is not yet well understood.

We consider the natural function of the PfCRT protein, the role of multiple genes and "genetic background" in the CQR mechanism, and the evolution of CQR in parasite populations. Genetic transformation techniques are improving in P. falciparum and continue to …

2016年3月31日 · Recent work has perfected yeast-based methods for measuring drug transport by the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT). The approach relies on inducible heterologous expression of PfCRT in Saccharomyces cerevisiae yeast.

2000年10月1日 · These data, transfection results, and selection of a CQR line harboring a novel K76I mutation point to a central role for the PfCRT protein in CQR. This transmembrane protein localizes to the parasite digestive vacuole (DV), the site of CQ action, where increased compartment acidification associates with PfCRT point mutations.

2001年10月23日 · The mechanistic basis for chloroquine resistance (CQR) in Plasmodium falciparum recently has been linked to the polymorphic gene pfcrt. Alleles associated with CQR in natural parasite isolates harbor threonine (T), as opposed to lysine (K) at amino acid 76.

pfcrt Mutations and the CQR Phenotype Are Perfectly Associated in a Set of Old World and New World Isolates. We identified pfcrt polymorphisms in the genetic cross by sequencing cDNA transcripts of Dd2, HB3, and two progeny, SC-01 (CQR) and GC-03 (CQS). Sequence comparisons revealed eight codon differences between the CQR and CQS clones at ...

2002年10月4日 · Here, we provide conclusive evidence that mutant haplotypes of the pfcrt gene product of Asian, African, or South American origin confer chloroquine resistance with characteristic verapamil reversibility and reduced chloroquine accumulation. pfcrt mutations increased susceptibility to artemisinin and quinine and minimally affected amodiaquine ac...