A lipophilic cation protects crops against fungal pathogens by multiple modes of action

The emerging resistance of crop pathogens to fungicides poses a challenge to food security and compels discovery of new antifungal compounds. Here, we show that mono-alkyl lipophilic cations (MALCs) inhibit oxidative phosphorylation by affecting NADH oxidation in the plant pathogens Zymoseptoria tritici , Ustilago maydis and Magnaporthe oryzae . One of these MALCs, consisting of a dimethylsulfonium moiety and a long alkyl chain (C 18 -SMe 2 + ), also induces production of reactive oxygen species at the level of respiratory complex I, thus triggering fungal apoptosis. In addition, C 18 -SMe 2 + activates innate plant defense. This multiple activity effectively protects cereals against Septoria tritici blotch and rice blast disease. C 18 -SMe 2 + has low toxicity in Daphnia magna , and is not mutagenic or phytotoxic. Thus, MALCs hold potential as effective and non-toxic crop fungicides. New fungicides are needed due to emerging resistance shown by crop pathogens. Here, the authors show that a mono-alkyl lipophilic cation protects plants from fungal pathogens by inhibiting fungal mitochondrial respiration, inducing production of reactive oxygen species, triggering fungal apoptosis, and activating innate plant defense.