Disruption of cell wall and membrane integrity as antioomycete and antifungal mode of action by fusaric and 9,10-dehydrofusaric acids from endophytic fungus Fusarium lactis strain SME13-2

Abstract Aims This study aimed to assess the mode of action of fusaric and 9,10-dehydrofusaric acids on cell respiration by measuring the hyphal oxygen consumption rate, and the effects on cell membrane integrity by determining the electrical conductivity of the mycelium. Methods and Results Bioactivity-directed fractionation of the active culture medium and mycelium organic extracts from the Fusarium lactis strain SME13-2 isolated from Sapium macrocarpum led to the isolation of two known alkylpicolinic acid derivatives: fusaric acid and 9,10-dehydrofusaric acid, along with the known polyketide bikaverin. Fusaric acid and 9,10-dehydrofusaric acid exhibited antioomycete and antifungal activities, significantly inhibiting the radial growth of Phytophthora capsici, Pythium aphanidermatum, Alternaria alternata, and F. oxysporum. Additionally, they induced changes in colony morphology and negative effects on the ultrastructure of their hyphae. To date, the antimicrobial mode of action of fusaric acid and other alkylpicolinic acid derivatives is not thoroughly understood. Therefore, we investigated their effect on cellular respiration by measuring the oxygen consumption rate of the hyphae and their impact on cell membrane integrity by determining the electrical conductivity of the mycelium. Fusaric and 9,10-dehydrofusaric acids inhibited the respiration of the mycelium and altered the permeability of the cell membrane in the tested phytopathogenic microorganisms in a concentration and exposure time-dependent manner, exerting a greater effect on oomycetes. The disruption of cell membrane integrity resulted in the leakage of cytoplasmic electrolytes into the extracellular medium, which, coupled with respiratory inhibition, could lead to cell death. Conclusions Fusaric and 9,10-dehydrofusaric acids show potential for the development of new fungicides and anti-oomycetes agents.