H2S-mediated protein S-sulfhydration modulates infectivity and autophagy in the rice blast fungus.

Hydrogen sulfide (HS) regulates cellular activities in plants and mammals through S-sulfhydration, a post-translational modification of proteins. The role of HS and its molecular targets in fungi, however, remains unclear. Here we show that HS, synthesized by cystathionine γ-lyase (CSE1) in the rice blast fungus Magnaporthe oryzae, is essential for optimal fungal infection. Excessive HS, through S-sulfhydration, impairs fungal infectivity by inhibiting autophagy. Using quantitative proteomics, we identify numerous S-sulfhydrated proteins in M. oryzae, including the autophagy-related protein ATG18. S-sulfhydration of a cysteine residue (Cys78) in ATG18 is essential for its binding to phosphatidylinositol 3-phosphate, thereby maintaining the protein's structural stability and regulating autophagy. Thus, our study reveals a mechanism by which HS-mediated S-sulfhydration controls autophagy in the rice blast fungus and suggests the potential use of HS donors as a strategy to control fungal diseases by targeting fungal development and infection structures.