A Transcriptomic Study of the Effects of Tea Tree Essential Oil on the Pathogenicity of Candida albicans

Candida albicans is a common opportunistic pathogen. Long-term use of azole antifungals faces challenges like resistance, necessitating novel agents. Tea tree oil (TTO), a natural broad-spectrum antimicrobial, shows promise, but its molecular mechanisms, particularly concerning novel cell death pathways, require clarification. This study comprehensively evaluated the antifungal mechanism of TTO against C. albicans using transcriptomics. Antifungal susceptibility assays were conducted to assess the effects of TTO and its components (4-terpineol, terpenes, and γ-pinene) on the growth of C. albicans hyphae and biofilms. Fluorescent labeling and biochemical analysis were employed to detect ferroptosis markers. Transcriptomic results indicate that TTO induces 423 differentially expressed genes and systematically inhibits the development of C. albicans hyphae through mechanisms such as oxidative stress, iron homeostasis disruption, disruption of cell wall integrity, and interference with ergosterol metabolism. Notably, the significant enrichment of redox enzyme activity and iron ion binding functions, along with changes in the glutathione metabolic pathway, suggest that ferroptosis may be involved in this process. Subsequent studies revealed that the compound 4-pinene most effectively inhibits the pathogenicity of C. albicans by suppressing its adhesion, hyphae formation, and biofilm formation, whereas terpinene induces the accumulation of reactive oxygen species (ROS) and increases lipid peroxidation in C. albicans; furthermore, following treatment with an iron-mediated apoptosis inhibitor, terpinene enhances the viability of the treated C. albicans cells.