The malaria parasite Plasmodium falciparum Vps15 is a Phosphatidylinositol 3-kinase interactor important for host-cell cytosol delivery to the food vacuole and apicoplast and mitochondrion dynamics.

Authors

Alexandra Bourgeois, Louis-David Martin, Harpreet Kaur, Dominic Gagnon, Joel B Dacks, Dave Richard

Published in

PLoS pathogens. Volume 22. Issue 8. Pages e1014526. Aug 18, 2026. Epub Aug 18, 2026.

Abstract

The malaria parasite Plasmodium alciparumf is an obligate intracellular organism that spends an important part of its lifecycle inside human erythrocytes. The endocytosis of host-cell cytosol and its delivery to a lysosome-like organelle called the food vacuole are critical for the parasite's survival and proliferation. Recent work has started to identify some of the molecular players involved in this pathway, but much remains to be discovered. Evidence suggests that phosphatidylinositol-3-phosphate (PI3P) plays a central role in this process. In unicellular eukaryotes, such as yeast, PI3P is generated by a single PI3-kinase, whose activity is regulated by a pseudokinase called Vps15. P. falciparum also possesses a PI3K that generates PI3P and bioinformatics analysis has revealed the presence of an uncharacterized putative orthologue of Vps15. We here present our characterization of PfVps15. We first show that it is constitutively expressed throughout the asexual erythrocytic cycle and that it interacts with PfPI3K, but unlike in yeast and mammalian cells, it is potentially not part of a heterotetrameric complex. The removal of PfVps15 from its site of action by knock sideways led to rapid parasite death. Phenotypic analyses revealed a decrease in PI3P levels, the abrogation of the delivery of host-cell cytosol containing vesicles to the food vacuole, and defects in apicoplast biogenesis and mitochondrial fission. Collectively, our data has identified a protein critical for the synthesis of PI3P and provides molecular evidence for the importance of this lipid in the vesicular trafficking pathway of host-cell cytosol, and apicoplast and mitochondrion dynamics.

PMID:
42611934
Bibliographic data and abstract were imported from PubMed on 19 Aug 2026.

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