Nanobiosensing and Microfluidic Point-of-Care Testing Key Laboratory of LuZhou, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.
School of Basic Medical Science, Southwest Medical University, Luzhou, People's Republic of China.
Virulence. 2024 Dec;15(1):2404256. doi: 10.1080/21505594.2024.2404256. Epub 2024 Sep 16.
is an opportunistic fungal pathogen that can cause systemic infections in immunocompromised individuals. Morphological transition and biofilm formation are major virulence factors of . Moreover, biofilm enhances resistance to antifungal agents. Therefore, it is urgent to identify new and effective compounds to target the biofilm of . In the present study, the antifungal activities of equol against were investigated. , the microdilution analysis and spot assay result showed that equol exhibited potent inhibitory activities against . Further investigations confirmed that the antifungal effects of equol involved interference with the transition from yeast to hypha and biofilm formation of . In addition, transcriptome sequencing and reverse transcription-quantitative PCR (qRT-PCR) analysis showed that equol significantly downregulated the expression of several genes in the Ras1-cAMP-PKA pathway related to hyphae and biofilm formation and significantly upregulated the expression of the negative transcriptional repressors and . Moreover, equol effectively reduced the production of cAMP, a key messenger in the Ras1-cAMP-PKA pathway, while supplementation with cAMP partly rescued the equol-induced defects in hyphal development. Furthermore, in a mouse model of systemic candidiasis (SC), equol treatment significantly decreased the fungal burden (liver, kidneys, and lung) in mice and local tissue damage, while enhancing the production of interleukin-10 (IL-10). Together, these findings confirm that equol is a potentially effective agent for treatment of SC.
是一种机会性真菌病原体,可导致免疫功能低下个体发生全身感染。形态转变和生物膜形成是 的主要毒力因子。此外,生物膜增强了对抗真菌药物的耐药性。因此,迫切需要识别新的有效化合物来靶向 的生物膜。在本研究中,研究了大豆苷元对 的抗真菌活性。微量稀释分析和点样试验结果表明,大豆苷元对 表现出很强的抑制活性。进一步的研究证实,大豆苷元的抗真菌作用涉及干扰从酵母到菌丝的转变和生物膜的形成。此外,转录组测序和逆转录定量聚合酶链反应 (qRT-PCR) 分析表明,大豆苷元显著下调与菌丝和生物膜形成相关的 Ras1-cAMP-PKA 途径中的几个基因的表达,并显著上调负转录抑制剂 和 的表达。此外,大豆苷元有效地降低了 Ras1-cAMP-PKA 途径中的关键信使 cAMP 的产生,而 cAMP 的补充部分挽救了大豆苷元诱导的菌丝发育缺陷。此外,在系统性念珠菌病 (SC) 的小鼠模型中,大豆苷元处理显著降低了小鼠肝脏、肾脏和肺部的真菌负荷和局部组织损伤,同时增强了白细胞介素-10 (IL-10) 的产生。总之,这些发现证实大豆苷元是治疗 SC 的潜在有效药物。