Carvacrol reduces virulence traits in meyerozyma guilliermondii and Candida dubliniensis and Enhances Galleria mellonella survival during Candidozyma auris infection

Background: Antifungal resistance among Candida species and related genera, coupled with the lack of new drugs, poses a significant threat to public health. Several studies have demonstrated a relationship between virulence factors and resistance. Current objectives include identifying new targets and searching for new natural molecules. Carvacrol, a natural phenolic compound, has been shown to have antimicrobial properties; however, its impact on the virulence of species other than Candida albicans and related yeast genera remains underexplored. Methods: The antifungal activity of carvacrol was evaluated against clinical isolates of Candidozyma auris, Meyerozyma guilliermondii, and Candida dubliniensis, as well as its effect on adhesion, hydrophobicity, biofilm formation and osmotic stress tolerance. In vivo activity was assessed using the Galleria mellonella infection model at MIC concentrations. Results: Carvacrol inhibited adherence and significantly reduced both early and preformed biofilms in M. guilliermondii and C. dubliniensis. In C. auris, the compound produced a modest reduction in biofilm activity but significantly enhanced larval survival in the in vivo model (~20%, p < 0.01). Carvacrol also induced increased tolerance of C. auris to osmotic stress, suggesting activation of adaptive pathways. Conclusions: Carvacrol exhibits species-specific effects, acting as an antivirulence modulator in M. guilliermondii and C. dubliniensis and attenuating virulence in vivo in C. auris. These findings support the potential of carvacrol as an adjuvant antifungal strategy, particularly against C. auris, and highlight the relevance of targeting virulence traits to reduce selective pressure and limit antifungal resistance.