External Lipid PI3P Mediates Entry of Eukaryotic Pathogen Effectors into Plant and Animal Host Cells

SummaryPathogens of plants and animals produce effector proteins that are transferred into the cytoplasm of host cells to suppress host defenses. One type of plant pathogens, oomycetes, produces effector proteins with N-terminal RXLR and dEER motifs that enable entry into host cells. We show here that effectors of another pathogen type, fungi, contain functional variants of the RXLR motif, and that the oomycete and fungal RXLR motifs enable binding to the phospholipid, phosphatidylinositol-3-phosphate (PI3P). We find that PI3P is abundant on the outer surface of plant cell plasma membranes and, furthermore, on some animal cells. All effectors could also enter human cells, suggesting that PI3P-mediated effector entry may be very widespread in plant, animal and human pathogenesis. Entry into both plant and animal cells involves lipid raft-mediated endocytosis. Blocking PI3P binding inhibited effector entry, suggesting new therapeutic avenues.

Graphical AbstractFigure optionsDownload high-quality image (92 K)Download as PowerPoint slideHighlights▸ Oomycete and fungal pathogen effectors bind PI3P via their host cell entry motifs ▸ PI3P is abundant on the surface of plant cells and some human cells ▸ Binding to PI3P is required for host cell entry via lipid raft-mediated endocytosis ▸ Blocking of effector entry by exogenous molecules suggests therapeutic strategies