Sensing of a spore surface protein by a Drosophila chemosensory protein induces behavioral defense against fungal parasitic infections.

In addition to innate immunity in a physiological context, insects have evolved behavioral defenses against parasite attacks. Here, we report that Drosophila can sense the CFEM (common in fungal extracellular membrane) protein Mcdc9, which acts as a negative virulence factor of the entomopathogenic fungus Metarhizium robertsii. The individual deletions of 18 CFEM genes in Metarhizium followed by fly infection identified three null mutants that could kill the flies more quickly than the wild-type strain, among which Mcdc9 can coat fungal spores and interact with the fly chemosensory protein CheA75a. The deletion of Mcdc9 in the fungus or the knockdown of CheA75a in flies had a similar effect, in which a greater number of fungal spores were left on flies than on the respective controls after topical infection. Thus, similar to the accelerated death of the wild-type flies treated with ΔMcdc9, the CheA75aRNAi flies succumbed more quickly than the control insects topically challenged with the wild-type strain. The CheA75a gene is highly transcribed in fly legs and wings, and positive electrophysiological responses were evidenced in tarsal sensilla after stimulation with the Mcdc9 protein. The results imply that this CFEM protein could be sensed as a contact elicitor inducing the hygienic behavior of flies against fungal parasitic infection, which reveals a previously unsuspected mechanism of fungus-insect interactions.