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.

病原性真菌可以克服对杀虫剂的抗药性，是控制蚊子的有前途的工具。更好地了解真菌-蚊子的相互作用对于提高真菌功效至关重要。昆虫表皮诱导后，致病真菌会发生明显的感染相关形态分化。但是，对真菌感染相关形态发生的调控机制了解甚少。在这里，我们表明，组蛋白赖氨酸甲基KMT2在绿僵robertsii（MrKMT2）在上调角质层感应。MrKMT2通过上调转录因子基因Mrcre1在调节感染相关的形态和致病性中起关键作用蚊子角质层感染过程中通过H3K4三甲基化作用。MrCre1进一步调节角质层诱导基因Mrhyd4，以调节感染结构（appressorium）的形成和毒力。总体而言，MrKMT2-MrCre1-MrHyd4调节途径调节感染相关的形态发生和致病M. robertsii。这些发现表明表观遗传调控机制在调节昆虫真菌发病机理中起着关键作用，并为致病真菌与昆虫宿主之间的分子相互作用提供了新的见解。