Chloroquine Transport via the Malaria Parasite’s Chloroquine Resistance Transporter

  title={Chloroquine Transport via the Malaria Parasite’s Chloroquine Resistance Transporter},
  author={Rowena E. Martin and Rosa Marchetti and Anna I. Cowan and Susan M. Howitt and Stefan Br{\"o}er and Kiaran Kirk},
  pages={1680 - 1682}
Malaria Chloroquine Resistance Transporter Malaria is one of the most deadly infectious diseases in the world today, and the emergence and spread of chloroquine-resistant parasites has been a disaster for world health. The Chloroquine Resistance Transporter (PfCRT) was originally identified because mutations in this protein confer chloroquine resistance in the human malaria parasite, Plasmodium falciparum. However, the mechanism by which they do so has been the subject of ongoing debate. Martin… 
Simplified Reversed Chloroquines To Overcome Malaria Resistance to Quinoline-Based Drugs
Data from in vitro heme binding and β-hematin inhibition assays suggest that the single aromatic RCQ compounds retain activities against Plasmodium falciparum similar to those of CQ, although other mechanisms of action may be relevant to their activities.
Antiplasmodial Cyclodecapeptides from Tyrothricin Share a Target with Chloroquine
These targets related to CQ antagonism, changes in neural lipid distribution, leading to hemozoin malformation, indicate that the tyrothricin cyclodecapeptides and CQ share a target in the malaria parasite.
Iron is a substrate of the Plasmodium falciparum chloroquine resistance transporter PfCRT in Xenopus oocytes
The data suggest that PfCRT might play a role in iron homeostasis, which is essential for the parasite's development in erythrocytes, and the ability to transport ferrous iron is reduced by the specific polymorphisms acquired by the Pf CRT variant as a result of chloroquine selection.
The malaria parasite’s chloroquine resistance transporter: An exploration of its interactions with drugs and of its evolution as a drug transporter
The malaria parasite’s ‘chloroquine resistance transporter’, PfCRT, and the next generation of quinoline-based strategies, including a ‘resistance stalemate’ strategy, are studied.
Role of Plasmodium falciparum transporters in drug resistance
Results point to the fact that the parasite susceptibility towards CQ and QN is regulated by phosphorylation, although the exact molecular mechanism needs to be further examined.
The Biochemistry of Quinoline Antimalarial Drug Resistance
Mutations in the Plasmodium falciparum chloroquine-resistance transporter (PfCRT) have been shown to be central to the molecular mechanism of quinoline antimalarial drug resistance. However,
Exploring the Plasmodium falciparum Transcriptome Using Hypergeometric Analysis of Time Series (HATS)
Exploring the Plasmodium falciparum Transcriptome Using Hypergeometric Analysis of Time Series (HATS) using hypergeometric analysis of time series data for the first time.
Chloroquine: modes of action of an undervalued drug.
Glutathione transport: a new role for PfCRT in chloroquine resistance.
PfCRT has a dual role in CQR, facilitating both efflux of harmful CQ from the DV and influx of beneficial GSH into the DV, which mediates the lower susceptibility to CQ in the PfCRT mutant parasites.


Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine
Evidence for an emerging focus of AQ resistance in Tanzania and the persistence of 4-aminoquinoline-resistant parasites in South America suggest that different histories of drug use on the two continents have driven the selection of distinct suites of pfcrt and pfmdr1 mutations.
Know your enemy: understanding the role of PfCRT in drug resistance could lead to new antimalarial tactics
It is suggested that PfCRT can be viewed both as a ‘multidrug-resistance carrier’ and as a drug target, and that the quinoline-res resistance mechanism is a potential ‘Achilles’ heel’ of the parasite.
Xenopus laevis Oocytes.
  • S. Bröer
  • Biology
    Methods in molecular biology
  • 2010
This chapter provides an overview of the basic methods used for the analysis of membrane transporters in this system, including preparation of oocytes, assays of transport activity, protocols for immunostaining and fluorescence microscopy, and other assays to study surface expression.
Differences in trans‐stimulated chloroquine efflux kinetics are linked to PfCRT in Plasmodium falciparum
The data are interpreted in favour of a carrier for chlorquine being present in both chloroquine‐sensitive and ‐resistant parasites, however, with different transport modalities.
Dissecting the loci of low‐level quinine resistance in malaria parasites
Results identify additive QTL in segments of chromosomes (Chrs) 13, 7 and 5, and pairwise effects from two additional loci of Chrs 9 and 6 that interact, respectively, with the QTL of ChRS 13 and 7.
The pH of the digestive vacuole of Plasmodium falciparum is not associated with chloroquine resistance
The results suggest that there is no significant difference in digestive vacuole pH of chloroquin-sensitive and chloroquine-resistant parasites, and that digestive vacUole pH does not play a primary role in chloroquines resistance.
Defining the role of PfCRT in Plasmodium falciparum chloroquine resistance
Transfection studies have now proven that pfcrt mutations confer verapamil‐reversible chloroquine resistance in vitro and reveal their important role in resistance to quinine.
Evidence for a pfcrt-associated chloroquine efflux system in the human malarial parasite Plasmodium falciparum.
Evidence is presented for an association of those pfcrt alleles found in chloroquine-resistant P. falciparum strains with the phenomenon of stimulated chlorquine accumulation under varying-trans conditions, interpreted in terms of a model in which pfCrt is directly or indirectly involved in carrier-mediated chloroquines efflux from resistant cells.
Trafficking of the Phosphoprotein PfCRT to the Digestive Vacuolar Membrane in Plasmodium falciparum
The data establish PfCRT as a phosphoprotein and suggest that phosphorylation of threonine 416 is a possible deciding signal for the sorting of Pf CRT to the digestive vacuolar membrane.