Mycotoxin-driven proteome remodeling reveals limited activation of Triticum aestivum responses to emerging chemotypes integrated with fungal modulation of ergosterols

Fusarium head blight (FHB), mainly caused by Fusarium graminearum, is a globally important wheat disease reducing yield and grain quality. The pathogen produces mycotoxins deoxynivalenol (DON), 3-acetyl DON (3ADON), 15-acetyl DON (15ADON), and nivalenol (NIV), which threaten food and feed safety. During the past 15 years, surveillance has identified nove trichothecenes 3ANX and NX, which show increased virulence compared to DON. In this study, we investigated the effects of 15ADON/3ANX chemotype on both wheat and F. graminearum proteomes to identify proteins and pathways responsive to the emerging mycotoxin chemotype. We defined a core wheat proteome across all strains (15ADON- and 15ADON/3ANX-producing, and untreated controls) to explore changes in protein abundance associated with defense response, grain development, and reduced photosynthesis upon infection. Conversely, we identified 32 wheat proteins exclusively produced in the presence of 15ADON/3ANX strains, providing further insight into chemotype-specific responses of wheat. Additionally, assessment from the fungal perspective, reported 119 proteins exclusive to the 15ADON/3ANX strains, including those associated with virulence and mycotoxin production. Lastly, investigation of strain-specific proteome changes showed a significant reduction in mycotoxin protective mechanisms in wheat upon exposure to two 15ADON/3ANX strains, as well as a novel connection between elevated ergosterol biosynthesis and 15ADON/3ANX producing strains. Together, our study characterizes distinct protein production profiles in wheat and F. graminearum in response to 3ANX and provides evidence that these molecular changes influence fungal virulence and host defense responses.