Abstract
The yeast-to-hypha transition plays a crucial role in the pathogenesis of C. albicans. Farnesol, a quorum sensing molecule (QSM) secreted by the fungal itself, could prevent the formation of hyphae and subsequently lead to the defect of biofilm formation. The DPP3, encoding phosphatase, is a key gene in regulating farnesol synthesis. In this study, we screened 24 bisbibenzyls and 2 bibenzyls that were isolated from bryophytes or chemically synthesized by using CLSI method for antifungal effect. Seven bisbibenzyls were found to have antifungal effects with IC80 less than 32 µg/ml, and among them, plagiochin F, isoriccardin C and BS-34 were found to inhibit the hyphae and biofilm formation of C. albicans in a dose-dependent manner. To uncover the underlying relationship between morphogenesis switch and QSM formation, we measured the farnesol production by HPLC-MS and quantified Dpp3 expression by detecting the fluorescent intensity of green fluorescent protein tagged strain using Confocal Laser Scanning microscopy and Multifunction Microplate Reader. The DPP3 transcripts were determined by real-time PCR. The data indicated that the bisbibenzyls exerted antifungal effects through stimulating the synthesis of farnesol via upregulation of Dpp3, suggesting a potential antifungal application of bisbibenzyls. In addition, our assay provides a novel, visual and convenient method to measure active compounds against morphogenesis switch.
Highlights
Candida albicans, which can change from symbiotic form to pathogenic form upon an alteration in the external environment, causes shallow surface infections as well as deep infections [1]
Antifungal activity of mycelium growth and biofilm formation We evaluated the activity of A1, A3 and A5 against morphological conversion and biofilm formation of C. albicans
Our lab previously reported that bisbibenzyls including plagiochin E and riccardin D derived from bryophytes displayed a moderate antifungal action [33,34]
Summary
Candida albicans, which can change from symbiotic form to pathogenic form upon an alteration in the external environment, causes shallow surface infections as well as deep infections [1]. The over use of wide-spectrum antibiotics, long and repeated treatment have caused pathogenic fungi resistant to antifungal agents, especially to fungistatic drugs [2], and thereby more effective therapeutic drugs or alternative treatments are needed to alleviate the situation. Studies have demonstrated that filamentation plays a crucial role in the pathogenic process [3,4,5]. The transition from yeast to hyphae could improve the virulence of C. albicans during the course of infection [6]. Hyphae serving as the skeleton of biofilms play a critical role for the formation of highly heterogeneous architecture, which protects microorganisms from antibiotic treatment and creates a source of persistent infection [7,8,9]. Prevention of the hyphae formation could be an effective means to reduce the biofilm formation and virulence in the pathogenesis of C. albicans
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