Evidence map›Paper›PMID 20451492›Full record

ArticleBiochimica et biophysica acta2010

Altered plasmodial surface anion channel activity and in vitro resistance to permeating antimalarial compounds.

Godfrey Lisk, Margaret Pain, Morgan Sellers, Philip A Gurnev, Ajay D Pillai, Sergey M Bezrukov, Sanjay A Desai

Abstract read
In one paragraph

Article in Biochimica et biophysica acta, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
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  8. Review
  9. The conserved clag multigene family of malaria parasites: essential roles in host-pathogen interaction.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2015
    Review
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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

7 authors at 1 institution in 1 country.

Godfrey LiskThe Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
Margaret Pain
Morgan Sellers
Philip A Gurnev
Ajay D Pillai
Sergey M Bezrukov
Sanjay A Desai
National Institutes of Health · US

Funding

Biophysics of Large Membrane ChannelsZIAHD000072 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI BEZRUKOV, SERGEY M · 2009 to 2025
$22.8M
The Plasmodial Surface Anion Channel And Malaria Parasite Nutrient AcquisitionZIAAI000882 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DESAI, SANJAY A · 2009 to 2025
$20.5M
Intramural NIH HHS ZIA AI000882
6 · The paper itself

Abstract

Erythrocytes infected with malaria parasites have increased permeability to various solutes. These changes may be mediated by an unusual small conductance ion channel known as the plasmodial surface anion channel (PSAC). While channel activity benefits the parasite by permitting nutrient acquisition, it can also be detrimental because water-soluble antimalarials may more readily access their parasite targets via this channel. Recently, two such toxins, blasticidin S and leupeptin, were used to select mutant parasites with altered PSAC activities, suggesting acquired resistance via reduced channel-mediated toxin uptake. Surprisingly, although these toxins have similar structures and charge, we now show that reduced permeability of one does not protect the intracellular parasite from the other. Leupeptin accumulation in the blasticidin S-resistant mutant was relatively preserved, consistent with retained in vitro susceptibility to leupeptin. Subsequent in vitro selection with both toxins generated a double mutant parasite having additional changes in PSAC, implicating an antimalarial resistance mechanism for water-soluble drugs requiring channel-mediated uptake at the erythrocyte membrane. Characterization of these mutants revealed a single conserved channel on each mutant, albeit with distinct gating properties. These findings are consistent with a shared channel that mediates uptake of ions, nutrients and toxins. This channel's gating and selectivity properties can be modified in response to in vitro selective pressure.

Indexed as

AnionsAntimalarialsCell Membrane PermeabilityDrug ResistanceErythrocyte MembraneIon Channel GatingIon ChannelsMutationPlasmodium falciparumAnionsAntimalarialsIon Channels

Identifiers

PMID20451492
PMCPMC2906662
OpenAlexW1977414554

What OpenQuestion holds

Textmetadata
LicenceTDM
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.