Evidence map›Paper›PMID 27189525›Full record

ArticleNature communications2016

Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies.

M Isabel Veiga, Satish K Dhingra, Philipp P Henrich, Judith Straimer, Nina Gnädig, Anne-Catrin Uhlemann, Rowena E Martin, Adele M Lehane, David A Fidock

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
201citing papers in PubMed, 5 pooled it
25.1field-weighted citation impact, top 1% 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

201 citing papers in PubMed, 5 syntheses or guidelines pooled it, 343 citations in OpenAlex.

  1. Pooled it
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  15. AbioRxiv : the preprint server for biology · 2026
    Article
  16. Article
  17. Reversal of Chloroquine Resistance inInternational journal of molecular sciences · 2026
    Article
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  20. Article

141 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 2 countries.

M Isabel VeigaDepartment of Microbiology and Immunology, Columbia University Medical Center, Room 1502 HHSC, 701 West 168th Street, New York, New York 10032, USA.
Satish K DhingraDepartment of Microbiology and Immunology, Columbia University Medical Center, Room 1502 HHSC, 701 West 168th Street, New York, New York 10032, USA.
Philipp P HenrichDepartment of Microbiology and Immunology, Columbia University Medical Center, Room 1502 HHSC, 701 West 168th Street, New York, New York 10032, USA.
Judith StraimerDepartment of Microbiology and Immunology, Columbia University Medical Center, Room 1502 HHSC, 701 West 168th Street, New York, New York 10032, USA.
Nina GnädigDepartment of Microbiology and Immunology, Columbia University Medical Center, Room 1502 HHSC, 701 West 168th Street, New York, New York 10032, USA.
Anne-Catrin UhlemannDivision of Infectious Diseases, Department of Medicine, Columbia University Medical Center, Box 82, 630 West 168th Street, New York, New York 10032, USA.
Rowena E MartinResearch School of Biology, Linnaeus Way, The Australian National University, Acton Australian Capital Territory 2601, Australia.
Adele M LehaneDepartment of Microbiology and Immunology, Columbia University Medical Center, Room 1502 HHSC, 701 West 168th Street, New York, New York 10032, USA.
David A FidockDepartment of Microbiology and Immunology, Columbia University Medical Center, Room 1502 HHSC, 701 West 168th Street, New York, New York 10032, USA.
Columbia University Irving Medical Center · USAustralian National University · AU

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
Defining P. falciparum resistance to artemisinin-based combination therapiesR01AI109023 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FIDOCK, DAVID A · 2014 to 2025
$4.4M
Elucidating the molecular basis of piperaquine resistance in Plasmodium falciparumR01AI124678 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI David A Fidock · 2016 to 2026
$4.3M
NIAID NIH HHS R01 AI050234NIAID NIH HHS R01 AI109023NIAID NIH HHS R01 AI124678NIAID NIH HHS R37 AI050234
6 · The paper itself

Abstract

Antimalarial chemotherapy, globally reliant on artemisinin-based combination therapies (ACTs), is threatened by the spread of drug resistance in Plasmodium falciparum parasites. Here we use zinc-finger nucleases to genetically modify the multidrug resistance-1 transporter PfMDR1 at amino acids 86 and 184, and demonstrate that the widely prevalent N86Y mutation augments resistance to the ACT partner drug amodiaquine and the former first-line agent chloroquine. In contrast, N86Y increases parasite susceptibility to the partner drugs lumefantrine and mefloquine, and the active artemisinin metabolite dihydroartemisinin. The PfMDR1 N86 plus Y184F isoform moderately reduces piperaquine potency in strains expressing an Asian/African variant of the chloroquine resistance transporter PfCRT. Mutations in both digestive vacuole-resident transporters are thought to differentially regulate ACT drug interactions with host haem, a product of parasite-mediated haemoglobin degradation. Global mapping of these mutations illustrates where the different ACTs could be selectively deployed to optimize treatment based on regional differences in PfMDR1 haplotypes.

Indexed as

AntimalarialsArtemisininsATP-Binding Cassette, Sub-Family C ProteinsDrug Resistance, MicrobialDrug Therapy, CombinationGeographyHaplotypesMalariaMutationPlasmodium falciparumAntimalarialsartemisininArtemisininsATP-Binding Cassette, Sub-Family C ProteinsMdr1 protein, Plasmodium falciparum

Identifiers

PMID27189525
PMCPMC4873939
OpenAlexW2397788564

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.