title: Possible inhibitory molecular mechanism of farnesol on the development of fluconazole resistance in Candida albicans biofilm.
abstract: Candida albicans biofilm infections are usually treated with azole antifungals such as fluconazole. However, the development of resistance to this drug in C. albicans biofilms is very common, especially in immunocompromised individuals. The upregulation of the sterol biosynthetic pathway gene ERG and the efflux pump genes CDR and MDR may contribute to this azole tolerance in Candida species. We hypothesize that farnesol, an endogenous quorum sensing molecule with possible antimicrobial properties which is also the precursor of ergosterols in C. albicans, may interfere with the development of fluconazole resistance in C. albicans biofilms. To test this hypothesis, MICs were compared and morphology changes were observed by confocal laser scanning microscopy (CLSM) for farnesol-treated and -untreated and fluconazole-resistant groups. The expression of possible target genes (ERG11, ERG25, ERG6, ERG5, ERG3, ERG1, MDR1, CDR1, and CDR2) in biofilms was analyzed by reverse transcription-PCR (RT-PCR) and quantitative PCR (qPCR) to investigate the molecular mechanisms of the inhibitory effects of farnesol. The results showed a decreased MIC of fluconazole and thinner biofilms for the farnesol-treated group, indicating that farnesol inhibited the development of fluconazole resistance. The sterol biosynthetic pathway may contribute to the inhibitory effects of farnesol, as the transcription levels of the ERG11, ERG25, ERG6, ERG3, and ERG1 genes decreased in the farnesol-treated group.
authors: Institute of Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, Nanjing Medical University, Nanjing, China.
authors: Li-Hua
authors: LH
authors: Yu
authors: Xin
authors: X
authors: Wei
authors: Ming
authors: M
authors: Ma
authors: Xiao-Jun
authors: XJ
authors: Chen
authors: Shuang-Bo
authors: SB
authors: Xu
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000648:ultrastructure; D025141:Drug Resistance, Fungal / Q000187:drug effects / Q000235:genetics*; D005204:Farnesol / Q000494:pharmacology*; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000592:standards; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D005204:Farnesol; D015725:Fluconazole