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绿茶多酚表没食子儿茶素没食子酸酯通过损害淀粉样卷曲纤维组装并经由σ(E) 依赖性小RNA RybB下调生物膜调节因子CsgD来抑制大肠杆菌生物膜形成。

The green tea polyphenol EGCG inhibits E. coli biofilm formation by impairing amyloid curli fibre assembly and downregulating the biofilm regulator CsgD via the σ(E) -dependent sRNA RybB.

作者信息

Serra Diego O, Mika Franziska, Richter Anja M, Hengge Regine

机构信息

Institut für Biologie/Mikrobiologie, Humboldt-Universität zu Berlin, 10115, Berlin, Germany.

出版信息

Mol Microbiol. 2016 Jul;101(1):136-51. doi: 10.1111/mmi.13379. Epub 2016 May 6.

Abstract

In bacterial biofilms, which are often involved in chronic infections, cells are surrounded by a self-produced extracellular matrix that contains amyloid fibres, exopolysaccharides and other biopolymers. The matrix contributes to the pronounced resistance of biofilms against antibiotics and host immune systems. Being highly inflammatory, matrix amyloids such as curli fibres of Escherichia coli can also play a role in pathogenicity. Using macrocolony biofilms of commensal and pathogenic E. coli as a model system, we demonstrate here that the green tea polyphenol epigallocatachin gallate (EGCG) is a potent antibiofilm agent. EGCG virtually eliminates the biofilm matrix by directly interfering with the assembly of curli subunits into amyloid fibres, and by triggering the σ(E) cell envelope stress response and thereby reducing the expression of CsgD - a crucial activator of curli and cellulose biosynthesis - due to csgD mRNA targeting by the σ(E) -dependent sRNA RybB. These findings highlight EGCG as a potential adjuvant for antibiotic therapy of biofilm-associated infections. Moreover, EGCG may support therapies against pathogenic E. coli that produce inflammatory curli fibres along with Shigatoxin.

摘要

在通常与慢性感染有关的细菌生物膜中,细胞被自身产生的细胞外基质所包围,该基质包含淀粉样纤维、胞外多糖和其他生物聚合物。这种基质导致生物膜对抗生素和宿主免疫系统具有显著抗性。作为高度炎症性物质,基质淀粉样蛋白(如大肠杆菌的卷曲纤维)也可在致病性方面发挥作用。我们以共生和致病性大肠杆菌的大菌落生物膜作为模型系统,在此证明绿茶多酚表没食子儿茶素没食子酸酯(EGCG)是一种有效的抗生物膜剂。EGCG实际上通过直接干扰卷曲亚基组装成淀粉样纤维,并通过触发σ(E)细胞包膜应激反应,从而减少CsgD(卷曲和纤维素生物合成的关键激活因子)的表达,因为σ(E)依赖性小RNA RybB靶向csgD mRNA,进而消除生物膜基质。这些发现突出了EGCG作为生物膜相关感染抗生素治疗潜在佐剂的作用。此外,EGCG可能有助于对抗产生炎性卷曲纤维以及志贺毒素的致病性大肠杆菌的治疗。

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