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豌豆防御素d2对生物膜形成、结构及其抑制作用的表征

Characterization of Biofilm Formation and Structure and Their Inhibition by Pea Defensin d2.

作者信息

Corrêa-Almeida Caroline, Borba-Santos Luana P, Rollin-Pinheiro Rodrigo, Barreto-Bergter Eliana, Rozental Sonia, Kurtenbach Eleonora

机构信息

Laboratório de Biologia Molecular e Bioquímica de Proteínas, Programa de Biologia Molecular e Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brasil.

Laboratório de Biologia Celular de Fungos, Programa de Parasitologia e Biologia Celular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brasil.

出版信息

Front Mol Biosci. 2022 Jan 27;9:795255. doi: 10.3389/fmolb.2022.795255. eCollection 2022.

Abstract

Approximately four million people contract fungal infections every year in Brazil, primarily caused by . 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. d2 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 biofilm formation and determined the effect of d2 on biofilms. After 4 hours, conidia adhered to polystyrene surfaces and formed a robust extracellular matrix-producing biofilm at 24 h, increasing thickness until 48 h d2 inhibited biofilm formation in a dose-dependent manner. Most notably, at 10 μM d2 inhibited 50% of biofilm viability and biomass and 40% of extracellular matrix production. d2 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 biofilm suggests a potential use of d2 as a prototype to design new antifungal agents to prevent biofilm formation by and related species.

摘要

在巴西,每年约有400万人感染真菌感染,主要由……引起。这些真菌在组织和医疗设备中形成生物膜的能力使治疗变得复杂,并导致免疫功能低下患者的高发病率和死亡率。d2是一种5.4 kDa的豌豆防御素,对代表性致病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(如葡糖神经酰胺和麦角固醇)的相互作用。在本研究中,我们对……生物膜的形成进行了表征,并确定了d2对……生物膜的影响。4小时后,……分生孢子附着在聚苯乙烯表面,并在24小时形成了一个强大的产生细胞外基质的生物膜,厚度持续增加直至48小时。d2以剂量依赖的方式抑制……生物膜的形成。最值得注意的是,在10 μM时,d2抑制了50%的生物膜活力和生物量以及40%的细胞外基质产生。d2显著减少了生物膜定殖的表面积,并改变了其组织结构水平,导致菌丝长度和直径缩短以及分生孢子梗形成受到抑制。这种针对……生物膜的活性表明,d2有可能作为设计新型抗真菌剂的原型,以防止……及相关物种形成生物膜。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1ed/8830917/729c986a208e/fmolb-09-795255-g001.jpg

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