Evidence map›Paper›PMID 25691625›Full record

ArticleAntimicrobial agents and chemotherapy2015

The Mu subunit of Plasmodium falciparum clathrin-associated adaptor protein 2 modulates in vitro parasite response to artemisinin and quinine.

Gisela Henriques, Donelly A van Schalkwyk, Rebekah Burrow, David C Warhurst, Eloise Thompson, David A Baker, David A Fidock, Rachel Hallett, Christian Flueck, Colin J Sutherland

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

32 citing papers in PubMed, 51 citations in OpenAlex.

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  18. Modification ofAntimicrobial agents and chemotherapy · 2019
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  20. Mutations inProceedings of the National Academy of Sciences of the United States of America · 2018
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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

10 authors at 3 institutions in 2 countries.

Gisela HenriquesDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Donelly A van SchalkwykDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Rebekah BurrowDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
David C WarhurstDepartment of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Eloise ThompsonDepartment of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
David A BakerDepartment of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
David A FidockDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York, USA Division of Infectious Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Rachel HallettDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Christian FlueckDepartment of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Colin J SutherlandDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom Department of Clinical Parasitology, Hospital for Tropical Diseases, University College London Hospital, London, United Kingdom Colin.sutherland@lshtm.ac.uk.
London School of Hygiene & Tropical Medicine · GBColumbia University · USHospital for Tropical Diseases · GB

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
NIAID NIH HHS R01 AI050234NIAID NIH HHS R01 AI109023NIAID NIH HHS R01 AI50234NIAID NIH HHS R37 AI050234
6 · The paper itself

Abstract

The emergence of drug-resistant parasites is a serious threat faced by malaria control programs. Understanding the genetic basis of resistance is critical to the success of treatment and intervention strategies. A novel locus associated with antimalarial resistance, ap2-mu (encoding the mu chain of the adaptor protein 2 [AP2] complex), was recently identified in studies on the rodent malaria parasite Plasmodium chabaudi (pcap2-mu). Furthermore, analysis in Kenyan malaria patients of polymorphisms in the Plasmodium falciparum ap2-mu homologue, pfap2-mu, found evidence that differences in the amino acid encoded by codon 160 are associated with enhanced parasite survival in vivo following combination treatments which included artemisinin derivatives. Here, we characterize the role of pfap2-mu in mediating the in vitro antimalarial drug response of P. falciparum by generating transgenic parasites constitutively expressing codon 160 encoding either the wild-type Ser (Ser160) or the Asn mutant (160Asn) form of pfap2-mu. Transgenic parasites carrying the pfap2-mu 160Asn allele were significantly less sensitive to dihydroartemisinin using a standard 48-h in vitro test, providing direct evidence of an altered parasite response to artemisinin. Our data also provide evidence that pfap2-mu variants can modulate parasite sensitivity to quinine. No evidence was found that pfap2-mu variants contribute to the slow-clearance phenotype exhibited by P. falciparum in Cambodian patients treated with artesunate monotherapy. These findings provide compelling evidence that pfap2-mu can modulate P. falciparum responses to multiple drugs. We propose that this gene should be evaluated further as a potential molecular marker of antimalarial resistance.

Indexed as

Adaptor Proteins, Vesicular TransportArtemisininsDNA, ComplementaryOpen Reading FramesPlasmodium falciparumProtein SubunitsQuinineReal-Time Polymerase Chain ReactionAdaptor Proteins, Vesicular TransportartemisininArtemisininsDNA, ComplementaryProtein SubunitsQuinine

Identifiers

PMID25691625
PMCPMC4394773
OpenAlexW2131276058

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.