PXD065766

PXD065766 is an original dataset announced via ProteomeXchange.

Title	Invasion preferences suggest a possible role for Plasmodium falciparum parasites in the expansion of Duffy negativity in West and Central Africa
Description	Duffy antigen receptor for chemokines (DARC) is the primary red blood cell (RBC) receptor for invasion of human RBCs by Plasmodium vivax and Plasmodium knowlesi merozoites. By contrast, Plasmodium falciparum parasites, which are the dominant cause of malaria in West and Central Africa, use multiple RBC receptors for invasion. Whether DARC is one of these receptors has never been systematically explored. We used flow cytometry and microscopy-based approaches to investigate whether P. falciparum parasites preferentially invade specific Duffy RBC phenotypes and explored two potential explanations for invasion preference – differences in RBC membrane biophysical properties and surface protein composition – using flickering spectroscopy and mass spectrometry. P. falciparum parasites showed a consistent preference for Duffy-positive RBCs, and some biophysical properties and membrane proteins varied between Duffy-positive and Duffy-negative RBCs. We then used our in vitro invasion data to parametrise an evolutionary-epidemiological model of the relationship between P. falciparum and the allele responsible for Duffy negativity (FYBES). Our model accounts for immunity against P. falciparum virulence, gained through exposure, and thus mutations that impede infection are not always advantageous. The inhibition of P. falciparum invasion that we observed in vitro leads to FYBES frequencies increasing at low levels of P. falciparum transmission but decreasing at high levels of P. falciparum transmission. The impact of P. falciparum on the prevalence of Duffy negativity may therefore be most apparent in lower P. falciparum transmission settings. Our findings reveal a link between Duffy negativity and P. falciparum for the first time and suggest that the DARC receptor may be directly or indirectly involved in P. falciparum invasion of human RBCs which could, together with P. vivax, explain the distribution of Duffy negativity in sub-Saharan Africa.
HostingRepository	PRIDE
AnnounceDate	2026-03-02
AnnouncementXML	Submission_2026-03-01_16:06:43.733.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robin Antrobus
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-03 16:42:48	ID requested
⏵ 1	2026-03-01 16:06:44	announced

10.1093/molbev/msag033;

Manneh B, Introini V, Reed J, Rotariu M, Antrobus R, Cicuta P, Weekes MP, Penman BS, Rayner JC, Invasion preferences suggest a possible role for Plasmodium falciparum parasites in the expansion of Duffy negativity in West and Central Africa. Mol Biol Evol, 43(2):(2026) [pubmed]

submitter keyword: plasma membrane profiling, RBC surface proteome, Duffy-negative RBC surface proteome,TMT

Professor Julian C. Rayner
contact affiliation	Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK
contact email	jcr1003@cam.ac.uk
lab head
Robin Antrobus
contact affiliation	CIMR medicine
contact email	pra29@cam.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/03/PXD065766

PRIDE project URI

• PRIDE
  1. PXD065766
     1. Label: PRIDE project
     2. Name: Invasion preferences suggest a possible role for Plasmodium falciparum parasites in the expansion of Duffy negativity in West and Central Africa