Coordinated regulation of infection-related morphogenesis by the KMT2-Cre1-Hyd4 regulatory pathway to facilitate fungal infection

Entomopathogenic fungi can overcome insecticide resistance and represent promising tools for the control of mosquitoes. Better understanding of fungus-mosquito interactions is critical for improvement of fungal efficacy. Upon insect cuticle induction, pathogenic fungi undergo marked infection-related morphological differentiation. However, regulatory mechanisms of fungal infection-related morphogenesis are poorly understood. Here, we show that a histone lysine methyltransferase KMT2 in Metarhizium robertsii (MrKMT2) is up-regulated upon cuticle induction. MrKMT2 plays crucial roles in regulating infection-related morphogenesis and pathogenicity by up-regulating the transcription factor gene Mrcre1 via H3K4 trimethylation during mosquito cuticle infection. MrCre1 further regulates the cuticle-induced gene Mrhyd4 to modulate infection structure (appressorium) formation and virulence. Overall, the MrKMT2-MrCre1-MrHyd4 regulatory pathway regulates infection-related morphogenesis and pathogenicity in M. robertsii. These findings reveal that the epigenetic regulatory mechanism plays a pivotal role in regulating fungal pathogenesis in insects, and provide new insights into molecular interactions between pathogenic fungi and insect hosts.