Inhibitory activity of hinokitiol against biofilm formation in fluconazole-resistant Candida species.
The aim of this study was to investigate the ability of hinokitiol to inhibit the formation of Candida biofilms. Biofilm inhibition was evaluated by quantification of the biofilm metabolic activity with XTT assay. Hinokitiol efficiently prevented biofilm formation in both fluconazole-susceptible and fluconazole-resistant strains of Candida species. We determined the expression levels of specific genes previously implicated in biofilm development of C. albicans cells by real-time RT-PCR. The expression levels of genes associated with adhesion process, HWP1 and ALS3, were downregulated by hinokitiol. Transcript levels of UME6 and HGC1, responsible for long-term hyphal maintenance, were also decreased by hinokitiol. The expression level of CYR1, which encodes the component of signaling pathway of hyphal formation-cAMP-PKA was suppressed by hinokitiol. Its upstream general regulator RAS1 was also suppressed by hinokitiol. These results indicate that hinokitiol may have therapeutic potential in the treatment and prevention of biofilm-associated Candida infections.
Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul, Korea.
Dae Jin
DJ
Kim
Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul, Korea.
Min Woo
MW
Lee
Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul, Korea.
Jeong Su
JS
Choi
Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul, Korea.
Seung Gwan
SG
Lee
Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jee Yoon
JY
Park
Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul, Korea.
Suhng Wook
http://orcid.org/0000-0001-5522-0447
SW
Kim
D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002175:Candida / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects; D041221:Candida glabrata / Q000187:drug effects; D041022:Candida tropicalis / Q000187:drug effects; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D039821:Monoterpenes / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D014334:Tropolone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000935:Antifungal Agents; D039821:Monoterpenes; D014334:Tropolone; D015725:Fluconazole; C009479:beta-thujaplicin