A parasitic fungus employs mutated eIF4A to survive on rocaglate-synthesizing <i>Aglaia</i> plants.

Abstract

Plants often generate secondary metabolites as defense mechanisms against parasites. Although some fungi may potentially overcome the barrier presented by antimicrobial compounds, only a limited number of examples and molecular mechanisms of resistance have been reported. Here, we found an <i>Aglaia</i> plant-parasitizing fungus that overcomes the toxicity of rocaglates, which are translation inhibitors synthesized by the plant, through an amino acid substitution in a eukaryotic translation initiation factor (eIF). <i>De novo</i> transcriptome assembly revealed that the fungus belongs to the <i>Ophiocordyceps</i> genus and that its eIF4A, a molecular target of rocaglates, harbors an amino acid substitution critical for rocaglate binding. Ribosome profiling harnessing a cucumber-infecting fungus, <i>Colletotrichum orbiculare</i>, demonstrated that the translational inhibitory effects of rocaglates were largely attenuated by the mutation found in the <i>Aglaia</i> parasite. The engineered <i>C. orbiculare</i> showed a survival advantage on cucumber plants with rocaglates. Our study exemplifies a plant-fungus tug-of-war centered on secondary metabolites produced by host plants.