Activity of Sanguinarine against Candida albicans Biofilms

Abstract

Candida albicans biofilms show resistance to many clinical antifungal agents and play a considerable contributing role in the process of C. albicans infections. New antifungal agents against C. albicans biofilms are sorely needed. The aim of this study was to evaluate sanguinarine (SAN) for its activity against Candida albicans biofilms and explore the underlying mechanism. The MIC 50 of SAN was 3.2 g/ ml, while Ն0.8 g/ml of SAN could suppress C. albicans biofilms. Further study revealed that Ն0.8 g/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 of C. albicans to SAN suppressed the expression of some adhesion-and hypha-specific/essential genes related to the cyclic AMP (cAMP) pathway, including ALS3, HWP1, ECE1, HGC1, and CYR1. Consistently, the endogenous cAMP level of C. albicans was 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 (IC 50 ) being 7.8 g/ml. Collectively, the results show that SAN exhibits strong activity against C. albicans biofilms, and the activity was associated with its inhibitory effect on adhesion and hypha formation due to cAMP pathway suppression.

RETRACTED: Sanguinarine Inhibits Mono- and Dual-Species Biofilm Formation by Candida albicans and Staphylococcus aureus and Induces Mature Hypha Transition of C. albicans

“…The results of the present study showed that sanguinarine gave potent antifungal activity against C. albicans SC5314 and S. aureus CMCC26003 single culture, with a MIC of 4 μg/mL, whereas, dual cultures of sanguinarine showed a MIC of 8 μg/mL. These results are consistent with previous reports indicating that sanguinarine exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria, and antifungal activity against Candida and dermatophytes [19].…”

“…Mature hyphae of C. albicans SC5314, in the presence of 8 µg/mL of sanguinarine, were shortened and obviously converted into the yeast state, which can be attributed to the reversible morphological plasticity of C. albicans SC5314 between yeast and hyphal forms in response to sanguinarine. Recently, Zhong et al assessed the toxicity of sanguinarine using human umbilical vein endothelial cells (HUVECs) and found that the half-maximal (50%) inhibitory concentration (IC50) of sanguinarine on HUVECs was 7.8 µg/mL and sanguinarine at the concentration over than 12.8 µg/mL began to induce observed toxic effect toward the mammalian cells [19]. The results indicated that sanguinarine exerted a weaker suppressive effect on mammalian cells than on C. albicans cells.…”

“…Sanguinarine, a benzophenanthridine alkaloid extracted from plants belonging to the family Papaveracea, elicits a wide range of biological effects, including anti-inflammatory and anti-cancer properties [15][16][17]. Interestingly, sanguinarine was found to be a potent inhibitor of S. aureus, Escherichia coli and Psoroptes cuniculi, and it was found to have anti-biofilm activity against C. albicans [18][19][20]. However, the inhibitory and scavenging effects of sanguinarine on S. aureus mono-species, and dual-species biofilms of C. albicans and S. aureus, as well as its influence on mature hypha of C. albicans remains to be fully elucidated.…”

Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans

“…Yeast-to-hyphae morphogenesis. Effects of PPIs combined with FLC on the yeast-to-hyphae morphogenesis of resistant C. albicans (CA10) were studied in a microplate-based assay 46 . In this assay, OME was selected as the representative PPI, and yeast-to-hyphae morphogenesis was induced by RPMI-1640.…”

The Synergistic Antifungal Effect and Potential Mechanism of D-Penicillamine Combined With Fluconazole Against Candida albicans

“…The sessile minimum inhibitory concentration (sMIC) of PCA combined with FLC against C. albicans was evaluated as described by Ramage et al (2001) and Zhong et al (2017) with moderate modifications. In this experiment, CA4, CA8, CA10, and CA16, four C. albicans strains with different FLC susceptibility levels were used to determine the sMIC of biofilms.…”