Antifungal mechanism of ketone volatile organic compounds against <i>Pseudogymnoascus destructans</i>

Ketone volatile organic compounds have demonstrated favorable inhibitory activity against a wide range of pathogenic fungi, including <i>Pseudogymnoascus destructans</i> (<i>Pd</i>), 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 <i>Pd</i> treated with 2-undecanone and 2-nonanone, aiming to investigate the effects of these ketones on the gene expression profiles of <i>Pd</i>. The results indicated that 2-undecanone and 2-nonanone inhibit spore germination in <i>Pd</i> 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 <i>Pd</i> 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 <i>Pd</i> DNA, triggering the activation of DNA damage repair mechanisms. This study provides a theoretical basis for exploring novel antifungal strategies targeting <i>Pd</i>, suggesting that ketones may serve as potential in vitro defense and control tools, laying the groundwork for the subsequent development of efficient fumigants.