Evidence map›Paper›PMID 39312588›Full record

ArticlePLoS pathogens2024

Application of optical tweezer technology reveals that PfEBA and PfRH ligands, not PfMSP1, play a central role in Plasmodium falciparum merozoite-erythrocyte attachment.

Emma Kals, Morten Kals, Rebecca A Lees, Viola Introini, Alison Kemp, Eleanor Silvester, Christine R Collins, Trishant Umrekar, Jurij Kotar, Pietro Cicuta and 1 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
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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

11 authors.

Emma KalsCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-2321-3661
Morten KalsCavendish Laboratory, University of Cambridge, Cambridge, United Kingdom.
Rebecca A LeesInstitute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London, United Kingdom.
Viola IntroiniCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Alison KempCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Eleanor SilvesterCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Christine R CollinsMalaria Biochemistry Laboratory, The Francis Crick Institute, London, United Kingdom.
Trishant UmrekarInstitute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London, United Kingdom.
Jurij KotarCavendish Laboratory, University of Cambridge, Cambridge, United Kingdom.
Pietro CicutaCavendish Laboratory, University of Cambridge, Cambridge, United Kingdom.
Julian C RaynerCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-9835-1014

Funding

Wellcome Trust
6 · The paper itself

Abstract

Malaria pathogenesis and parasite multiplication depend on the ability of Plasmodium merozoites to invade human erythrocytes. Invasion is a complex multi-step process involving multiple parasite proteins which can differ between species and has been most extensively studied in P. falciparum. However, dissecting the precise role of individual proteins has to date been limited by the availability of quantifiable phenotypic assays. In this study, we apply a new approach to assigning function to invasion proteins by using optical tweezers to directly manipulate recently egressed P. falciparum merozoites and erythrocytes and quantify the strength of attachment between them, as well as the frequency with which such attachments occur. Using a range of inhibitors, antibodies, and genetically modified strains including some generated specifically for this work, we quantitated the contribution of individual P. falciparum proteins to these merozoite-erythrocyte attachment interactions. Conditional deletion of the major P. falciparum merozoite surface protein PfMSP1, long thought to play a central role in initial attachment, had no impact on the force needed to pull merozoites and erythrocytes apart, whereas interventions that disrupted the function of several members of the EBA-175 like Antigen (PfEBA) family and Reticulocyte Binding Protein Homologue (PfRH) invasion ligand families did have a significant negative impact on attachment. Deletion of individual PfEBA and PfRH ligands reinforced the known redundancy within these families, with the deletion of some ligands impacting detachment force while others did not. By comparing over 4000 individual merozoite-erythrocyte interactions in a range of conditions and strains, we establish that the PfEBA/PfRH families play a central role in P. falciparum merozoite attachment, not the major merozoite surface protein PfMSP1.

Indexed as

ErythrocytesMalaria, FalciparumOptical TweezersPlasmodium falciparumAntigens, ProtozoanHumansLigandsMerozoitesMerozoite Surface Protein 1Protozoan ProteinsAntigens, ProtozoanLigandsMerozoite Surface Protein 1Protozoan Proteins

Identifiers

PMID39312588
PMCPMC11449297

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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.