PDF(Pubmed)
Abstract：
Approximately four million people contract fungal infections every year in Brazil, primarily caused by Aspergillus spp. The ability of these fungi to form biofilms in tissues and medical devices complicates treatment and contributes to high rates of morbidity and mortality in immunocompromised patients. Psd2 is a pea defensin of 5.4 kDa that possesses good antifungal activity against planktonic cells of representative pathogenic fungi. Its function depends on interactions with membrane and cell wall lipid components such as glucosylceramide and ergosterol. In the present study, we characterized Aspergillus nidulans biofilm formation and determined the effect of Psd2 on A. nidulans biofilms. After 4 hours, A. nidulans conidia adhered to polystyrene surfaces and formed a robust extracellular matrix-producing biofilm at 24 h, increasing thickness until 48 h Psd2 inhibited A. nidulans biofilm formation in a dose-dependent manner. Most notably, at 10 μM Psd2 inhibited 50% of biofilm viability and biomass and 40% of extracellular matrix production. Psd2 significantly decreased the colonized surface area by the biofilm and changed its level of organization, causing a shortening of length and diameter of hyphae and inhibition of conidiophore formation. This activity against A. nidulans biofilm suggests a potential use of Psd2 as a prototype to design new antifungal agents to prevent biofilm formation by A. nidulans and related species.
摘要：
在巴西，每年大约有400万人感染真菌感染，主要由曲霉属引起。这些真菌在组织和医疗装置中形成生物膜的能力使治疗复杂化,并导致免疫受损患者的高发病率和死亡率。Psd2是5.4kDa的豌豆防御素，对代表性病原真菌的浮游细胞具有良好的抗真菌活性。其功能取决于与膜和细胞壁脂质成分如葡萄糖神经酰胺和麦角甾醇的相互作用。在本研究中,我们表征了构巢曲霉生物膜的形成，并确定了Psd2对构巢曲霉生物膜的影响。4小时后,A.nidulans分生孢子粘附在聚苯乙烯表面，并在24小时形成强大的细胞外基质产生生物膜，增加厚度直到48小时Psd2以剂量依赖的方式抑制了A.nidulans生物膜的形成。最值得注意的是,在10μM下,Psd2抑制50%的生物膜活力和生物量以及40%的细胞外基质产生。Psd2显著降低生物膜的定植表面积，改变其组织水平，导致菌丝长度和直径缩短，并抑制分生孢子形成。这种针对邻道A.nidulans生物膜的活性表明Psd2作为设计新的抗真菌剂以防止邻道A.nidulans和相关物种形成生物膜的原型的潜在用途。
