Metabolomic profiles of the infection pathways of Calcarisporium cordycipiticola on the cultivated and medicinal mushroom, Cordyceps militaris.

Cordyceps militaris is a widely cultivated mushroom with multiple medicinal properties. However, the emergence of white mildew disease caused by Calcarisporium cordycipiticola has become a serious dilemma, leading to economic losses in its industrial production. The genome of Ca. cordycipiticola possesses more secondary metabolite biosynthetic gene clusters and a smaller number of genes encoding for carbohydrate-active enzyme secretion than other mycoparasites. To uncover those functional metabolites correlated with the infection process, metabolomic profiles between healthy C. militaris fruit bodies (CK) and healthy (HFB) and diseased (DFB) parts of infected C. militaris fruit bodies by Ca. cordicipiticola were compared based on untargeted metabolomic analyses. The function of different metabolites during the pathogen infection and host response processes were further analyzed according to their respective metabolic pathways. Results of key metabolic pathway analyses suggested that a sterigmatocystin-like metabolite functions as one of the virulence factors of white mildew disease on C. militaris, whereas S-adenosyl-L-methionine represents a hub intermediate in both processes of pathogen infection and host response, highlighting the relevance of methyl group turnovers in this battle. More importantly, the detection of toxic metabolites in diseased C. militaris fruiting bodies suggests that this macrofungus contaminated by Ca. cordycipiticola should not be consumed due to the risk that it may contain related instead toxins. This study hypothesizes on the scenario of key metabolic biosynthesis in the battle between Ca. cordycipiticola and C. militaris. Our instead findings not only shed light on the interaction between the pathogen and the host but also provide crucial insights for the development of effective prevention and control strategies in the future.