A binary-distributed effector modulates fungal host preference for drosophilids by targeting a lineage-specific immune factor

Unlike host-specific parasites, broad-spectrum pathogens often exhibit an enigmatic strain/race-level preference for infecting particular host species over others. Here, we identify a polymorphic effector (termed Bhe1) that exhibits a binary presence-absence distribution pattern among strains of the entomopathogenic fungus <i>Beauveria bassiana</i>. Gene deletion and overexpression in <i>Bhe1-</i>present strains revealed that this gene functions as a virulence factor against <i>Drosophila</i> species but dispensable for infection of mosquitoes, beetles, and locusts. Through targeted protein screening, we verified that Bhe1 targets a drosophilid-specific factor with an unknown function (termed Dsff1). The expression of <i>Dsff1</i> is induced in <i><i>Drosophila melanogaster</i></i> upon fungal infection and is controlled by the Toll pathway. Survival of <i>Dsff1</i> RNA interference (RNAi) flies was impaired after infection with the wild-type but not Δ<i>Bhe1</i> strain of <i>B. bassiana</i>. Overexpression of <i>Bhe1</i> and <i>Dsff1</i> in <i>D. melanogaster,</i> respectively, suppresses and promotes fly antifungal immunity. Further investigations reveal that Dsff1 binds Bombardier (Bbd), and Bhe1 blocks their interaction. Consistent with Bbd's role as a Toll-mediated immune factor, both <i>Dsff1</i> and <i>Bbd</i> RNAi flies exhibit similar defects in the secretion of immune factors, including antifungal peptides. While revealing the mechanistic control of parasite host preference, our identification of a novel immune factor in <i>Drosophila</i> underscores a compelling instance of host-parasite evolutionary arms race.