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Author Summary Fungi are a source of a large variety of carbohydrate-binding proteins (lectins). Synthesis of these proteins usually occurs in the cytoplasm and is often restricted to the reproductive organs (fruiting bodies, sclerotia) of the respective fungi. Although these lectins can be very abundant in these organs, their function is unknown. The specificity for non-fungal carbohydrates and recent functional studies in genetically amenable fungi argue against an endogenous function in development. Here we show that oral administration of the fruiting-body-specific galectins of the ink cap mushroom Coprinopsis cinerea is toxic for the model nematode Caenorhabditis elegans and that the nematotoxicity of these fungal lectins is dependent on binding to a specific β-galactoside occurring on nematode, but not on fungal, N-glycans. Since fungal-feeding nematodes represent the predominant predators of fungi in the soil, these results suggest that these lectins are effectors of a protein-mediated fungal defense system. Lectin-mediated defense strategies against predators, parasites and pathogens are also used by plants and animals. Due to the conservation of this type of innate defense amongst eukaryotes and the reduced complexity of fungi, studies of this in fungi could contribute to a better understanding of analogous systems and the evolution of multi-level defense in animals.
