Inhibition of RNase to Attenuate Fungal-Manipulated Rhizosphere Microbiome and Diseases.

Soil-borne pathogens must cross the barriers of plant-associated microbiota to cause disease. Phytopathogens utilize effector proteins to manipulate host immunity and promote niche colonization. Identifying core effectors involved in both pathogen-microbiota and pathogen-host interactions is vital for understanding pathogenic mechanisms and designing targeted chemical compounds for disease prevention. Here, this work shows that the soil-borne pathogen Fusarium graminearum can manipulate the plant-associated rhizosphere microbiome through the virulence effector Fg12, which encodes a fungal-specific ribonuclease (RNase). Fg12 is widely distributed among various fungal pathogens, and its antibacterial function relies on RNase activity. Several Fg12-inhibited bacterial strains, both individually and in synthetic communities (Syncoms), can alleviate Fusarium infection in soybean and alfalfa plants. Moreover, this work employs structural modeling, molecular docking, and in vitro enzymatic assays to demonstrate that guanosine monophosphate (GMP) functions as an effective chemical inhibitor of Fg12. Notably, GMP efficiently inhibits the antibacterial activity of Fg12 and alleviates disease symptoms in soybean and alfalfa. In conclusion, this work demonstrates that a virulence effector of a fungal phytopathogen can interfere with the host microbiome and propose GMP as a promising RNase inhibitor for attenuating plant fungal diseases.