title: Activity of Sanguinarine against Candida albicans Biofilms.
abstract: Candida albicansbiofilms show resistance to many clinical antifungal agents and play a considerable contributing role in the process ofC. albicansinfections. New antifungal agents againstC. albicansbiofilms are sorely needed. The aim of this study was to evaluate sanguinarine (SAN) for its activity againstCandida albicansbiofilms and explore the underlying mechanism. The MIC50of SAN was 3.2 μg/ml, while ≥0.8 μg/ml of SAN could suppressC. albicansbiofilms. Further study revealed that ≥0.8 μg/ml of SAN could decrease cellular surface hydrophobicity (CSH) and inhibited hypha formation. Real-time reverse transcription-PCR (RT-PCR) results indicated that the exposure ofC. albicansto SAN suppressed the expression of some adhesion- and hypha-specific/essential genes related to the cyclic AMP (cAMP) pathway, includingALS3,HWP1,ECE1,HGC1, andCYR1Consistently, the endogenous cAMP level ofC. albicanswas downregulated after SAN treatment, and the addition of cAMP rescued the SAN-induced filamentation defect. In addition, SAN showed relatively low toxicity to human umbilical vein endothelial cells, the 50% inhibitory concentration (IC50) being 7.8 μg/ml. Collectively, the results show that SAN exhibits strong activity againstC. albicansbiofilms, and the activity was associated with its inhibitory effect on adhesion and hypha formation due to cAMP pathway suppression.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhong
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Hu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.|Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
authors.forename: Gan-Hai
authors.initials: GH
authors.lastname: Hu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Bi
authors.affiliation: Shanghai Center of Biomedicine Development, Shanghai, China.
authors.forename: Zhuo-Er
authors.initials: ZE
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Ri-Li
authors.initials: RL
authors.lastname: Zhang
authors.affiliation: Faculty of Health Service, Second Military Medical University, Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China jiangyuanying@126.com wangyansmmu@126.com.
authors.forename: Yuan-Ying
authors.initials: YY
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China jiangyuanying@126.com wangyansmmu@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D053119:Benzophenanthridines / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D025301:Hyphae / Q000187:drug effects* / Q000235:genetics; D007546:Isoquinolines / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D053119:Benzophenanthridines; D007546:Isoquinolines; C005705:sanguinarine; D000242:Cyclic AMP
keywords: Candida albicans; antibiofilm; sanguinarine