关键词: Candida auris Baicalein Biofilm Virulence

Mesh : Flavanones / pharmacology Virulence Factors / metabolism genetics Animals Antifungal Agents / pharmacology Candida auris / drug effects genetics Microbial Sensitivity Tests Scutellaria baicalensis / chemistry Candidiasis / drug therapy microbiology Reactive Oxygen Species / metabolism Swine Larva / microbiology Moths / microbiology Biofilms / drug effects Plant Extracts / pharmacology Flavonoids

来  源:   DOI:10.1007/s00203-024-04038-9

Abstract:
Candida auris, a rapidly spreading multi-drug-resistant fungus, is causing lethal infections under certain conditions globally. Baicalin (BE), an active ingredient extracted from the dried root of Scutellaria baicalensis Georgi, exhibits antifungal activity. However, studies have shown the distinctive advantages of Traditional Chinese medicine in combating fungal infections, while the effect of BE, an active ingredient extracted from the dried roots of Scutellaria baicalensis Georgi, on C. auris, remains unknown. Therefore, this study aims to evaluate the potential of BE as an antifungal agent against the emerging multidrug-resistant C. auris. Various assays and models, including microbroth dilution, time growth curve analysis, spot assays, adhesion tests, flocculation test, cell surface hydrophobicity assay, hydrolase activity assays, XTT assay, violet crystal assay, scanning electron microscope (SEM), confocal laser scanning microscope (CLSM), flow cytometry, Live/dead fluorescent staining, reactive oxygen species (ROS), cell wall assay, aggregation assay, porcine skin model, Galleria mellonella larvae (G. mellonella larvae) infection model, and reverse transcription-quantitative polymerase chain reaction (RT-PCR) were utilized to investigate how baicalein suppresses C. auris through possible multifaceted mechanisms. The findings indicate that BE strongly inhibited C. auris growth, adhesion, and biofilm formation. It also effectively reduced drug resistance and aggregation by disrupting the cell membrane and cell wall while reducing colonization and invasion of the host. Transcriptome analysis showed significant modulation in gene expression related to different virulence factors post-BE treatment. In conclusion, BE exhibits significant effectiveness against C. auris, suggesting its potential as a viable treatment option due to its multifaceted suppression mechanisms.
摘要:
耳念珠菌,一种迅速传播的多重耐药真菌,在全球某些条件下导致致命的感染。黄芩苷(BE),从黄芩干根中提取的活性成分,具有抗真菌活性。然而,研究表明,中药在对抗真菌感染方面具有独特的优势,而BE的效果,从黄芩干根中提取的活性成分,关于C.auris,仍然未知。因此,本研究旨在评估BE作为抗真菌药物对抗新出现的多药耐药金黄色葡萄球菌的潜力。各种化验和模型,包括微量肉汤稀释,时间增长曲线分析,斑点测定,附着力试验,絮凝试验,细胞表面疏水性测定,水解酶活性测定,XTT测定,紫水晶试验,扫描电子显微镜(SEM),共聚焦激光扫描显微镜(CLSM),流式细胞术,活/死荧光染色,活性氧(ROS),细胞壁测定,聚集测定,猪皮肤模型,海绵状幼虫(G.Mellonella幼虫)感染模型,和逆转录定量聚合酶链反应(RT-PCR)用于研究黄芩素如何通过可能的多方面机制抑制C.auris。结果表明,BE强烈抑制了C.auris的生长,附着力,和生物膜的形成。它还通过破坏细胞膜和细胞壁,同时减少宿主的定植和侵袭,有效地减少了耐药性和聚集。转录组分析显示与BE处理后的不同毒力因子相关的基因表达的显着调节。总之,BE对C.auris表现出显著的有效性,由于其多方面的抑制机制,表明其作为可行的治疗选择的潜力。
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