A co-evolved peptide-GPCR system senses host entry to drive fungal infection.

A fungal GPCR-Pit2 system that detects host entry and promotes Ustilago maydis infection is conserved and structurally similar to mammalian GPCRs.

• Why it matters: Understanding how fungi sense host environments is crucial for developing strategies to prevent infections, yet fungal GPCR mechanisms remain poorly characterized compared to mammals.
• What they did: The study identified a GPCR-based sensing system in Ustilago maydis involving the secreted protein Pit2, which is cleaved by host proteases to release a peptide that activates the fungal GPCR Gpe1; the structure of Pit2 and its complex with Gpe1 was modeled and mutationally analyzed.
• The result: Disrupting the Gpe1/Pit2 interaction reduces fungal virulence, and the system’s conservation and mechanistic similarity to mammalian receptors suggest an evolutionary link, providing potential targets for antifungal strategies.