关键词: Cryptococcus neoformans biofilm formation niosomes phagocytosis phospholipase B1 propolis pulmonary cryptococcosis

Mesh : Humans Biofilms / drug effects Cell Line, Tumor Cryptococcosis / prevention & control therapy Cryptococcus neoformans / drug effects enzymology pathogenicity Ethanol / chemistry Fungal Proteins / antagonists & inhibitors Liposomes Lung Diseases, Fungal / prevention & control therapy Lysophospholipase / antagonists & inhibitors Macrophages, Alveolar / microbiology Propolis / chemistry pharmacology Virulence / drug effects Virulence Factors / antagonists & inhibitors Antifungal Agents / chemistry pharmacology

来  源:   DOI:10.3390/molecules28176224   PDF(Pubmed)

Abstract:
Secretory phospholipase B1 (PLB1) and biofilms act as microbial virulence factors and play an important role in pulmonary cryptococcosis. This study aims to formulate the ethanolic extract of propolis-loaded niosomes (Nio-EEP) and evaluate the biological activities occurring during PLB1 production and biofilm formation of Cryptococcus neoformans. Some physicochemical characterizations of niosomes include a mean diameter of 270 nm in a spherical shape, a zeta-potential of -10.54 ± 1.37 mV, and 88.13 ± 0.01% entrapment efficiency. Nio-EEP can release EEP in a sustained manner and retains consistent physicochemical properties for a month. Nio-EEP has the capability to permeate the cellular membranes of C. neoformans, causing a significant decrease in the mRNA expression level of PLB1. Interestingly, biofilm formation, biofilm thickness, and the expression level of biofilm-related genes (UGD1 and UXS1) were also significantly reduced. Pre-treating with Nio-EEP prior to yeast infection reduced the intracellular replication of C. neoformans in alveolar macrophages by 47%. In conclusion, Nio-EEP mediates as an anti-virulence agent to inhibit PLB1 and biofilm production for preventing fungal colonization on lung epithelial cells and also decreases the intracellular replication of phagocytosed cryptococci. This nano-based EEP delivery might be a potential therapeutic strategy in the prophylaxis and treatment of pulmonary cryptococcosis in the future.
摘要:
分泌型磷脂酶B1(PLB1)和生物膜作为微生物毒力因子,在肺隐球菌病中发挥重要作用。本研究旨在配制蜂胶负载的niosome(Nio-EEP)的乙醇提取物,并评估新生隐球菌PLB1生产和生物膜形成过程中发生的生物活性。类脂质体的一些物理化学特征包括球形的平均直径为270nm,zeta电位为-10.54±1.37mV,和88.13±0.01%的包封效率。Nio-EEP可以持续释放EEP,并在一个月内保持一致的理化性质。Nio-EEP具有渗透新生梭菌细胞膜的能力,导致PLB1mRNA表达水平显著下降。有趣的是,生物膜的形成,生物膜厚度,生物膜相关基因(UGD1和UXS1)的表达水平也显著降低。在酵母感染之前用Nio-EEP预处理使肺泡巨噬细胞中的新型梭状芽孢杆菌的细胞内复制减少了47%。总之,Nio-EEP作为抗毒剂介导抑制PLB1和生物膜的产生,以防止真菌在肺上皮细胞上定植,并减少吞噬隐球菌的细胞内复制。这种基于纳米的EEP递送可能是未来预防和治疗肺隐球菌病的潜在治疗策略。
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