Antifungal mechanism of ketone volatile organic compounds against Pseudogymnoascus destructans

Ketone volatile organic compounds have demonstrated favorable inhibitory activity against a wide range of pathogenic fungi, including Pseudogymnoascus destructans (Pd), the lethal pathogenic fungus responsible for white-nose syndrome in bats. However, the mechanism of fungal inhibition by ketones remains unclear. In this study, we employed transcriptomic analysis to conduct RNA sequencing on Pd treated with 2-undecanone and 2-nonanone, aiming to investigate the effects of these ketones on the gene expression profiles of Pd. The results indicated that 2-undecanone and 2-nonanone inhibit spore germination in Pd and cause significant damage to its mycelium. The minimum inhibitory concentrations (MIC) were determined to be 25.94 μg/mL and 135.41 μg/mL, respectively. Transcriptomic analysis revealed these ketones affects Pd through multiple pathways, inducing lesions in the cell wall and membrane, and disrupting ribosomal stability by interfering with rRNA modifications and ribosome assembly. Additionally, we found that 2-undecanone impacts enzymes involved in the tricarboxylic acid cycle, disrupting energy metabolism by interfering with critical metabolic pathways in aerobic organisms. In contrast, 2-nonanone directly damages Pd DNA, triggering the activation of DNA damage repair mechanisms. This study provides a theoretical basis for exploring novel antifungal strategies targeting Pd, suggesting that ketones may serve as potential in vitro defense and control tools, laying the groundwork for the subsequent development of efficient fumigants.