Fungal predatory behavior on nematodes has evolved independently in all major fungal lineages. The basidiomycete oyster mushroomPleurotus ostreatusis a carnivorous fungus that preys on nematodes to supplement its nitrogen intake under nutrient-limiting conditions. Its hyphae can paralyze nematodes within a few minutes of contact, but the mechanism had remained unclear. We demonstrate that the predator–prey relationship is highly conserved between multiplePleurotusspecies and a diversity of nematodes. To further investigate the cellular and molecular mechanisms underlying rapid nematode paralysis, we conducted genetic screens inCaenorhabditis elegansand isolated mutants that became resistant toP. ostreatus. We found that paralysis-resistant mutants all harbored loss-of-function mutations in genes required for ciliogenesis, demonstrating that the fungus induced paralysis via the cilia of nematode sensory neurons. Furthermore, we observed thatP. ostreatuscaused excess calcium influx and hypercontraction of the head and pharyngeal muscle cells, ultimately resulting in rapid necrosis of the entire nervous system and muscle cells throughout the entire organism. This cilia-dependent predatory mechanism is evolutionarily conserved inPristionchus pacificus, a nematode species estimated to have diverged fromC. elegans280 to 430 million y ago. Thus,P. ostreatusexploits a nematode-killing mechanism that is distinct from widely used anthelmintic drugs such as ivermectin, levamisole, and aldicarb, representing a potential route for targeting parasitic nematodes in plants, animals, and humans.

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