Backsround:The phenotypic switching of Candida spp.plays an important role in the development of vulvovaginal candidiasis (WC).Fesol,as a quorum-sensing molecule in Candida albicans,has the ability to prevent yeast-to-hyphal conversion in vitro.However,the mechanism underlying this ability is unclear.This study aimed to investigate changes in protein levels to better understand how fesol impacts processes contributing to WC.Methods:The isobaric tag for relative and absolute quantitation technique was used to detect protein expression in C.albicans strain SC5314 (ATCC MYA-2876) with or without fesol exposure.Proteins with a threshold fold change greater than 1.5 were screened and considered differentially expressed proteins.All the altered proteins were analyzed using Gene Ontology annotation,Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation,and metabolic pathway annotation.Results:Between the fesol-exposed group and the fesol-unexposd group,we detected 297 altered proteins among all 2047 tested proteins based on a threshold fold change of more than 1.5 (P ＜ 0.05).Eighty-seven of the 297 altered proteins exhibited metabolic enzyme activity and participated in 85 metabolic pathways according to KEGG pathway analysis.Most of these metabolic pathways were associated with central carbon metabolism processes.In the sterol synthesis pathway,which involves the synthesis of fesol,ERG25 (methylsterol monooxygenase) and ERG4 (delta 24(24(1))-sterol reductase) were both downregulated in the fesol-exposed group.All six altered proteases associated with the oxidative phosphorylation process were downregulated in the fesol-exposed group relative to the fesol-unexposed group.Conclusions:The mechanisms underlying fesol-induced phenotype switching involves the adjustment of metabolic activities and epigenetic modification.Exogenous fesol had an evident,but non-deterministic effect on the synthesis of ergosterol.The potential drug activity of fesol warrants further investigation.