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Magnolol As a Potent Antifungal Agent Inhibits Virulence Factors the PKC and Cek1 MAPK Signaling Pathways

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Abstract

Magnolol, a lignin compound extracted from Cortex, has been found to have prominent antifungal effects against . However, the specific mechanism still remains unclear. Therefore, this study aimed to further explore the inhibition mechanism of magnolol against virulence factors and the related signaling pathways. By an XTT reduction assay, a hyphal formation assay, confocal laser scanning microscopy, transmission electron microscopy, a calcofluor white staining assay, and a cell wall β-glucan quantitative detection assay, we evaluated the inhibitory effects of magnolol against the adhesion, hyphal formation, biofilm viability, biofilm spatial structure, and cell wall ultrastructure of . Moreover, by RNA sequencing and qRT-PCR, we confirmed the effects of magnolol in inhibiting the gene expression of virulence factors and the related signaling pathways. The results revealed that the adhesion and hyphal formation of were inhibited significantly by magnolol. The viability and spatial structures of biofilms were further weakened. ultrastructure showed partial thinning of cell walls and even rupture, with cytoplasmic leakage. The cell wall intergrity and β-glucan content were also radically reduced. Moreover, magnolol caused significant inhibition of the expression of adhesion, invasion, hyphal formation, biofilm formation, β-1,3-glucan synthesis, and hydrolase secretion-related genes, including , , , , , , , and . Furthermore, the PKC pathway-related genes (, , , , ) and Cek1 pathway-related genes (, , , ) were also significantly downregulated, indicating that the inhibition of magnolol against virulence factors might be related to PKC and Cek1 MAPK signaling pathways. In conclusion, the findings of this study confirmed the inhibition mechanism of magnolol against virulence factors, which might be related to PKC and Cek1 MAPK pathways, thus laying the theoretical foundation for its clinical antifungal applications.

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