Ethylenediaminetetraacetic Acid Disodium Salt Acts as an Antifungal Candidate Molecule against Fusarium graminearum by Inhibiting DON Biosynthesis and Chitin Synthase Activity

Fusarium fungi are the cause of an array of devastating diseases affecting yield losses and accumulating mycotoxins. Fungicides can be exploited against Fusarium and deoxynivalenol (DON) production. However, Fusarium resistance to common chemicals has become a therapeutic challenge worldwide, which indicates that new control agents carrying different mechanisms of action are desperately needed. Here, we found that a nonantibiotic drug, ethylenediaminetetraacetic acid disodium salt (EDTANa(2)), exhibited various antifungal activities against Fusarium species and DON biosynthesis. The infection of wheat seeding caused by F. graminearum was suppressed over 90% at 4 mM EDTANa(2). A similar control effect was observed in field tests. Mycotoxin production assays showed DON production was significantly inhibited, 47% lower than the control, by 0.4 mM EDTANa(2). In vitro experiments revealed a timely inhibition of H2O2 production as quickly as 4 h after amending cultures with EDTANa(2) and the expression of several TRI genes significantly decreased. Chitin synthases of Fusarium were Mn2+-containing enzymes that were strongly inhibited by Mn2+ deficiency. EDTANa(2) inhibited chitin synthesis and destroyed the cell wall and cytomembrane integrity of Fusarium, mainly via the chelation of Mn2+ by EDTANa(2), and thus led to Mn deficiency in Fusarium cells. Taken together, these findings uncover the potential of EDTANa(2) as a fungicide candidate to manage Fusarium head blight (FHB) and DON in agricultural production.

Automated summary

Fusarium fungi are responsible for devastating diseases affecting yield and mycotoxin production. Resistance to fungicides has become a global therapeutic challenge, highlighting the need for new control agents. The nonantibiotic drug EDTANa(2) was found to exhibit antifungal activities against Fusarium species and inhibit DON biosynthesis, making it a potential fungicide candidate for managing Fusarium head blight and DON in agriculture.