#Plasmodium

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FIKK1, a member of the FIKK kinase family, phosphorylates VAR2CSA and regulates adhesion of #Plasmodium falciparum-infected erythrocytes to the placental receptor CSA

by Benoît Gamain, Jean-Philippe Semblat, Heledd Eavis, Hugo Belda, Romain Hamelin, Clara-Eva Paquereau, Christian Doerig, Moritz Treeck, Dominique Dorin-Semblat #Plasmodium falciparum promotes the adhesion of infected erythrocytes (IEs) to host cells by extensively remodeling their surface. For this process, the parasite exports a large number of proteins to its host erythrocyte, including members of the P. falciparum Erythrocyte Membrane Protein-1 (PfEMP1) adhesin family and members of the FIKK family. Several FIKK have been shown to play a role in P. falciparum virulence, notably affecting IEs cell surface remodeling, rigidity and cytoadhesion. VAR2CSA, a member of the PfEMP1 adhesin family, is associated with IEs sequestration in the placenta and has been shown to be phosphorylated. In view of the previously described importance of VAR2CSA phosphorylation, we investigated the role of FIKK1. We show that FIKK1 is capable of phosphorylating VAR2CSA in vitro, and that this phosphorylation increases the binding of recombinant VAR2CSA to the placental receptor chondroitin sulphate A (CSA). In an inducible transgenic cell line expressing HA-tagged FIKK1, immunofluorescence assays indicate that the kinase localizes to punctuated foci within Maurer’s Cleft, similarly to VAR2CSA. Rapamycin-induced knock out of FIKK1 reduces IEs cytoadhesion to CSA, even though levels of VAR2CSA are not affected. In vitro phosphorylation assays show that FIKK1 can phosphorylate recombinant DBL1–3 domains on several residues, including S429 and T934, previously implicated in in vitro binding and IEs cytoadhesion to CSA. Taken together, these data support a model whereby FIKK1 contributes to placental malaria virulence through IEs sequestration mediated by VAR2CSA phosphorylation. Having no orthologs in mammals, this orphan kinase therefore represents an attractive target for the development of drugs against placental malaria.

dlvr.it

FIKK1, a member of the FIKK kinase family, phosphorylates VAR2CSA and regulates adhesion of #Plasmodium falciparum-infected erythrocytes to the placental receptor CSA

by Benoît Gamain, Jean-Philippe Semblat, Heledd Eavis, Hugo Belda, Romain Hamelin, Clara-Eva Paquereau, Christian Doerig, Moritz Treeck, Dominique Dorin-Semblat #Plasmodium falciparum promotes the adhesion of infected erythrocytes (IEs) to host cells by extensively remodeling their surface. For this process, the parasite exports a large number of proteins to its host erythrocyte, including members of the P. falciparum Erythrocyte Membrane Protein-1 (PfEMP1) adhesin family and members of the FIKK family. Several FIKK have been shown to play a role in P. falciparum virulence, notably affecting IEs cell surface remodeling, rigidity and cytoadhesion. VAR2CSA, a member of the PfEMP1 adhesin family, is associated with IEs sequestration in the placenta and has been shown to be phosphorylated. In view of the previously described importance of VAR2CSA phosphorylation, we investigated the role of FIKK1. We show that FIKK1 is capable of phosphorylating VAR2CSA in vitro, and that this phosphorylation increases the binding of recombinant VAR2CSA to the placental receptor chondroitin sulphate A (CSA). In an inducible transgenic cell line expressing HA-tagged FIKK1, immunofluorescence assays indicate that the kinase localizes to punctuated foci within Maurer’s Cleft, similarly to VAR2CSA. Rapamycin-induced knock out of FIKK1 reduces IEs cytoadhesion to CSA, even though levels of VAR2CSA are not affected. In vitro phosphorylation assays show that FIKK1 can phosphorylate recombinant DBL1–3 domains on several residues, including S429 and T934, previously implicated in in vitro binding and IEs cytoadhesion to CSA. Taken together, these data support a model whereby FIKK1 contributes to placental malaria virulence through IEs sequestration mediated by VAR2CSA phosphorylation. Having no orthologs in mammals, this orphan kinase therefore represents an attractive target for the development of drugs against placental malaria.

www.univadis.de

RKI warnt vor seltener Flughafenmalaria

Vier Beschäftigte des Frankfurter Flughafens haben sich mit Plasmodium falciparum infiziert. Das RKI rät bei Fieber ohne Reiseanamnese von Flughafenpersonal zu erhöhter Aufmerksamkeit.

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Analysis of the effect of primaquine dose on efficacy, safety, and tolerability in patients with Plasmodium vivax malaria in Ethiopia: a systematic review and individual patient data meta-analysis - Malaria Journal

Background The 8-aminoquinoline antimalarials are used to prevent P. vivax relapses. Recent evidence suggests high total dose primaquine (7 mg/kg) provides optimal efficacy, however, many countries,…

doi.org

Multiple mosquito species are potential competent vectors of avian malaria in the UK | Parasitology | Cambridge Core

Multiple mosquito species are potential competent vectors of avian malaria in the UK

dlvr.it

Regional Patterns and Temporal Trends of Pfdhfr and Pfdhps Markers of Antifolate Resistance in #Plasmodium falciparum in East and West Africa, 2010–2025: A Systematic Review

Publication date: Available online 12 July 2026 Source: Acta Tropica Author(s): Loise Ndung'u, Brenda Muriithi, Stephen Gitahi, Mathew Piero Ngugi, Daniel Kiboi