Role of epigenetic regulation of pathogenicity in the fungus Metarhizium brunneum - Galleria mellonella pathosystem

Entomopathogenic fungi (EPF) are important players in the integrated pest management aimed at minimizing the use of chemical pesticides which are harmful for both human and environment. The host-generalist EPF, Metarhizium brunneum, found to be a useful model organism for studying the factors affecting pathogenicity and virulence. In a previous study, we have shown intra-species variation in disease progression and pathogenicity in Myzus persicae aphids for M. brunneum isolates. We demonstrated that MbK is a more virulent isolate compared to Mb7. In the current study, we compared genomic, epigenetic and metabolomic variations between these isolates and their role in the varying pathogenicity. Differential N6-adenine methylation (6mA) between Mb7 and MbK along with negative correlation to expression in the essential swc4 gene (belonging to the SWR1 chromatin-remodeling complex) led us to hypothesize its role in the varying pathogenicity. Mutagenesis on swc4 gene and the non-essential swr1 gene in MbK isolate demonstrated reduced virulence towards the model host Galleria mellonella. Secondary metabolite (SM) analysis by LC-MS demonstrated high similarity between the swc4-mutant and Mb7 isolate. Toxicity assessment by injection into G. mellonella demonstrated that only MbK filtrate is able to cause mortality. Our results suggest the role of SWC4 subunit in the regulation of SMs and the role of the SWR1 complex in varying virulence in M. brunneum isolates. A better understanding of epigenetic regulation of pathogenicity and virulence in EPF may offer new venues for fungal manipulation for disease control in human, plants and insects.