Evidence map›Paper›PMID 26420308›Full record

ArticleScientific reports2015

Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, enlarge the parasite's food vacuole and alter drug sensitivities.

Serena Pulcini, Henry M Staines, Andrew H Lee, Sarah H Shafik, Guillaume Bouyer, Catherine M Moore, Daniel A Daley, Matthew J Hoke, Lindsey M Altenhofen, Heather J Painter and 7 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
7.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

  1. Pooled it
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  5. Review
  6. A Narrative Review on the Prevalence ofTropical medicine and infectious disease · 2025
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  9. Overexpression inFrontiers in cellular and infection microbiology · 2025
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  11. Bibliometric analysis of antimalarial drug resistance.Frontiers in cellular and infection microbiology · 2024
    Review
  12. Article
  13. Fighting Plasmodium chloroquine resistance with acetylenic chloroquine analogues.International journal for parasitology. Drugs and drug resistance · 2022
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Methods Used to Investigate theFrontiers in cellular and infection microbiology · 2021
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 8 institutions in 5 countries.

Serena PulciniInstitute for Infection and Immunity, St. George's, University of London, London SW17 0RE, UK.
Henry M StainesInstitute for Infection and Immunity, St. George's, University of London, London SW17 0RE, UK.
Andrew H LeeDepartment of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
Sarah H ShafikResearch School of Biology, Australian National University, Canberra, ACT 2601, Australia.
Guillaume BouyerInstitute for Infection and Immunity, St. George's, University of London, London SW17 0RE, UK.
Catherine M MooreInstitute for Infection and Immunity, St. George's, University of London, London SW17 0RE, UK.
Daniel A DaleyDepartment of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA.
Matthew J HokeDepartment of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA.
Lindsey M AltenhofenDepartment of Biochemistry and Molecular Biology and Center for Malaria Research, Pennsylvania State University, State College, Pennsylvania 16802, USA.
Heather J PainterDepartment of Biochemistry and Molecular Biology and Center for Malaria Research, Pennsylvania State University, State College, Pennsylvania 16802, USA.
Jianbing MuLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville MD 20852, USA.
David J P FergusonNuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Manuel LlinásDepartment of Biochemistry and Molecular Biology and Center for Malaria Research, Pennsylvania State University, State College, Pennsylvania 16802, USA.
Rowena E MartinResearch School of Biology, Australian National University, Canberra, ACT 2601, Australia.
David A FidockDepartment of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
Roland A CooperDepartment of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA.
Sanjeev KrishnaInstitute for Infection and Immunity, St. George's, University of London, London SW17 0RE, UK.
University of London · GBPennsylvania State University · USAustralian National University · AUColumbia University Irving Medical Center · USOld Dominion University · USDominican University of California · USJohn Radcliffe Hospital · GBNational Institutes of Health · US

Funding

Role of pfcrt in chloroquine resistance in P. falciparumR01AI050234 · NIAID · YESHIVA UNIVERSITY · PI FIDOCK, DAVID A · 2001 to 2015
$5.7M
Defining the Role of PfCRT and PfMDR1 as Pleiotropic Mediators of Plasmodium falciparum Multidrug ResistanceR37AI050234 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI David A Fidock · 2018 to 2026
$4.4M
Columbia University Graduate Training Program in Microbiology and ImmunologyT32AI106711 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Nicholas Arpaia, Uttiya Basu · 2014 to 2026
$2.1M
Determinants of growth and fitness in drug resistant malaria parasitesR01AI071121 · NIAID · UNIVERSITY OF NOTRE DAME · PI FERDIG, MICHAEL T · 2008 to 2012
$1.8M
NIAID NIH HHS R01 AI050234NIAID NIH HHS R01 AI071121NIAID NIH HHS R01 AI50234NIAID NIH HHS R37 AI050234NIAID NIH HHS T32 AI106711
6 · The paper itself

Abstract

Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, are the major determinant of chloroquine resistance in this lethal human malaria parasite. Here, we describe P. falciparum lines subjected to selection by amantadine or blasticidin that carry PfCRT mutations (C101F or L272F), causing the development of enlarged food vacuoles. These parasites also have increased sensitivity to chloroquine and some other quinoline antimalarials, but exhibit no or minimal change in sensitivity to artemisinins, when compared with parental strains. A transgenic parasite line expressing the L272F variant of PfCRT confirmed this increased chloroquine sensitivity and enlarged food vacuole phenotype. Furthermore, the introduction of the C101F or L272F mutation into a chloroquine-resistant variant of PfCRT reduced the ability of this protein to transport chloroquine by approximately 93 and 82%, respectively, when expressed in Xenopus oocytes. These data provide, at least in part, a mechanistic explanation for the increased sensitivity of the mutant parasite lines to chloroquine. Taken together, these findings provide new insights into PfCRT function and PfCRT-mediated drug resistance, as well as the food vacuole, which is an important target of many antimalarial drugs.

Indexed as

MutationAmino Acid SubstitutionAnimalsAntimalarialsBiological TransportChloroquineDrug ResistanceHumansMembrane Transport ProteinsOocytesParasitic Sensitivity TestsPlasmodium falciparumProtozoan ProteinsVacuolesXenopus laevisAntimalarialsChloroquineMembrane Transport ProteinsPfCRT protein, Plasmodium falciparumProtozoan Proteins

Identifiers

PMID26420308
PMCPMC4588581
OpenAlexW2195607601

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.