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

Abstract

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.

DIM5/KMT1 controls fungal insect pathogenicity and genome stability by methylation of histone H3K4, H3K9 and H3K36

“…The KMT1, KMT2 and KMT3 families play conserved roles in histone H3K9me, H3K4me and H3K36me in eukaryotes respectively [5]. In B. bassiana, our study clarified not only a conserved role of DIM5/KMT1 in H3K9me, as reported previously in S. pombe [15] and some filamentous fungi [38,44,45], but also its noncanonical activities to H3K4me and H3K36me, which are usually mediated by SET1/KMT2 [3,20,49] and SET2/ KMT3 [25][26][27] respectively. The three DIM5methylated H3 lysines had profound effect on the fungal lifecycle in vivo and in vitro, as discussed below.…”

“…Previously, H3K4me and H3K36me were reported as marks of the nucleosomes associated with transcription-active genes [28]. H3K4me1/me2/me3 abolished in the absence of kmt2/ set1 resulted in nearly equal number of genes up-or down-regulated (770:728) in M. robertsii [49]. The up/ down ratio (1.46) of dysregulated genes in the present study is far above the ratio (1.06) in the previous study, and closer to the up/down ratio (1.79) of 92 dysregulated genes encoding TFs and PTMs-required enzymes, which enable direct regulation of genome-wide gene expression.…”

“…The H3K_me-dependent gene expression and phenotypes are of special merits for the pest control potential of fungal insect pathogens since the potential relies upon fungal virulence, stress tolerance and developmental traits favoring massive production of qualified conidia as active ingredients of fungal insecticides [46][47][48]. In Metarhizium robertsii, abolishment of H3K4me by loss-of-function mutation of SET1/KMT2 resulted in blocked appressorial formation, compromised insect pathogenicity, and differential expression of 1,498 genes considered to be KMT2 dependent [49]. However, pleiotropic effect of H3K_me on the fungal potential against arthropod pests remains understood insufficiently.…”

Hydrophobin CmHYD1 Is Involved in Conidiation, Infection and Primordium Formation, and Regulated by GATA Transcription Factor CmAreA in Edible Fungus, Cordyceps militaris

“…grisea is regulated by nitrogen repression genes (NPR1 and NUT1) [ 25 ] and hydrophobin gene Mrhyd4 in Me. robertsii is regulated by a carbon catabolite repressor, MrCre1 [ 27 , 28 ]. It was suggested that a nutrition-linked regulatory mechanism may be involved in the regulation of hydrophobin genes.…”

“…In Me. robertsii , a zinc finger transcript factor MrCre1, termed a carbon catabolite repressor, was confirmed to regulate Mrhyd4, a class I hydrophobin, to modulate infection structure (appressorium) formation and virulence [ 27 , 28 ]. It was assumed that a nutrition-linked regulatory mechanism may be involved in the regulation of hydrophobin genes.…”