Subversion of Atypical Mucin Traps by a Spore-Coat Effector Blocks Cellular Immunity in Drosophila

While a few effectors of entomopathogenic fungi such as Metarhizium robertsii have been shown to evade insect humoral immunity, the strategies employed by fungi to subvert host cellular defenses remain elusive. Here, we report the identification of a spore-coat protein Eac1 in M. robertsii that is essentially required for fungal infection of drosophilids but not caterpillars. Eac1 targets Sgf1 (spore gluing factor), which interacts with its clustered homolog Sgf2 in Drosophila melanogaster. Both Sgf1 and Sgf2 are drosophilid-specific secreted proteins of previously unknown function. Unlike Sgf2, Sgf1 is patchily distributed among drosophilids and appears to be a duplicate of Sgf2. Both genes are induced via the Toll pathway following fungal infection. We demonstrate that Sgf1 and Sgf2 are small atypical mucins that bind fungal cell wall components and entrap spores by forming a colloidal-like gel matrix; however, this entrapment can be disrupted by Eac1. Null mutants of Sgf1, Sgf2, and especially the double mutants of Drosophila, were significantly impaired in their ability to combat fungal colonization. Our findings reveal that spore entrapment by atypical mucins is a prerequisite for effective hemocyte encapsulation and demonstrate how fungal parasites deploy a specialized coat protein to evade host cellular immunity.