Antifungal mechanisms of oregano essential oil against Aspergillus fumigatus

In this study, oregano essential oil (OEO) was identified from among six essential oils to be the most effective antifungal agent against Aspergillus fumigatus , with a minimum inhibitory concentration of 0.32 μL/mL. OEO significantly inhibited the growth of A. fumigatus , and altered the physiological characteristics. The electrical conductivity of the cultures, the intracellular malondialdehyde content, the fluorescence intensity indicative of the plasma membrane integrity, and the intracellular reactive oxygen species (ROS) significantly increased than those without OEO. In contrast, ATP content significantly decreased. An integrated transcriptomic and metabolomic analysis demonstrated that OEO treatment significantly reduced the levels of the membrane-associated lipids and TCA cycle intermediates in A. fumigatus . Concurrently, the 2-hydroxydecanedioic acid of the fatty acid oxidation product was decrease. Furthermore, these metabolic alterations were significantly correlated with the expression of the ten genes, including AFUA_1G16523, AFUA_6G02450, AFUA_8G05985, AFUA_3G11510, AFUA_7G01000, AFUA_5G14210, AFUA_1G09890, AFUA_5G00310, AFUA_5G00300, AFUA_7G01010. RT-qPCR results confirmed that their expression levels were significant difference compared to that without OEO, which were consistent with the transcriptomic data. Therefore, OEO inhibited A. fumigatus by coordinately regulating a core network of ten genes, which disrupted carbon and lipid metabolism, ultimately leading to the damage of the plasma membrane integrity and permeability, reduce of intracellular ATP levels, and ROS accumulation. This study constructed a comprehensive “gene-metabolite-phenotype” pathway map elucidating the inhibitory mechanism of OEO against A. fumigatus . • Oregano essential oil (OEO) inhibited the growth of A. fumigatus. • OEO damaged plasma membrane integrity and permeability. • OEO decreased intracellular ATP levels and increased intracellular ROS content. • OEO disrupted carbon and lipid metabolism in A. fumigatus.