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What makes a mycoparasite? Similarities between fungi that attack other fungi and fungal and oomycete plant pathogens based on structural homology of their candidate effectors

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Alexandros G. Sotiropoulos, Matthias Heuberger, Thomas Wicker, Levente Kiss

Summary

Researchers investigated whether mycoparasitic fungi use molecular strategies similar to plant pathogens by analyzing CAZyme profiles across 50+ fungal genomes and using AlphaFold to predict effector protein structures in three specialist mycoparasites, finding that CAZyme families AA3-2 and AA9 were associated with mycoparasitism and that predicted effector structures were homologous to known effectors in the plant pathogen Blumeria graminis.

<title>Abstract</title> Fungi that feed and thrive on other living fungi and damage those through specific adaptations to this lifestyle are known as mycoparasites. Despite its ecological significance and practical applications in crop protection, this type of parasitism is still poorly understood. Here, we hypothesize that aggressive fungal-fungal parasitic interactions are similar to those between plants and their fungal pathogens. We tested this hypothesis in two ways. First, we analyzed the genetic signatures of the mycoparasitic nutrition mode through the Carbohydrate-Active enZYme (CAZyme) profiles of more than 50 fungi with high-quality reference genomes across the Fungal Kingdom, including mycoparasites and their close relatives. Two CAZyme families, AA3-2 and AA9, appeared to be associated with mycoparasitism. Second, we searched for candidate effectors in protein datasets of three specialist mycoparasites and closely related fungi. Based on the tertiary structures of selected proteins predicted by AlphaFold, we identified protein clusters. Surprisingly, several tertiary structures predicted in all three, phylogenetically diverse mycoparasites were homologous to well-studied candidate effectors in a model plant pathogen, <italic>Blumeria graminis</italic>. One of these protein clusters belonged to the AA9 CAZyme family. These results supported our hypothesis and revealed a new approach to understand mycoparasitism at molecular level.

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