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探索革兰氏阳性病原体生物膜形成过程中 Sortase 作用的生物学和结构架构。

Exploring the Biology and Structural Architecture of Sortase Role on Biofilm Formation in Gram Positive Pathogens.

机构信息

School of Basic Science, Indian Institute of Technology, Mandi, Himachal Pradesh, India.

Department of Bioinformatics, Computer Aided Drug Design and Molecular Modeling Lab, Alagappa University, Science Block, Karaikudi- 630003, Tamilnadu, India.

出版信息

Curr Top Med Chem. 2018;18(29):2462-2480. doi: 10.2174/1568026619666181130133916.

Abstract

Gram-positive bacteria signify a surface organelle that decorates the cell surfaces using Sortase enzymes. The mechanism of SrtC links to the formation of amide or peptide bonds between cell surface proteins that sorting signal to strategically positioned amino groups. Sorting signals linked to peptidoglycan function as the principal architects of the cell wall and facilitate each microbe to effectively interact with its host environment. These enzymes play a fundamental role in microbial physiology and interestingly, sequence analysis on Gram-positive bacteria implies that approximately 60% of sortases are categorized into six families, and from that SrtA and SrtC are widely investigated in various literature. Sortase felicitates several functions that include adhesins, internalin's, blood clotting, immune evasion factors and transporters for nutrients across the microbial cell wall envelope. Recent evidence has proved that removal of Sortase genes tends to loss of host cell adhesion mechanism and inhibition of Biofilms. So that, blocking the Sortase enzyme is a powerful target and due to the receptor availability in all Gram-positive types, it is so called as a universal drug target for gram-positive pathogens. Sortase enzymes have been intensely studied for anti-infective studies and this review focus the mechanisms of surface protein anchoring to the cell wall envelope by sortases and highlight how it plays a strong role as a drug target.

摘要

革兰氏阳性菌表面的一种细胞器,利用 Sortase 酶对细胞表面进行装饰。SrtC 的作用机制是在细胞表面蛋白的特定位置的氨基之间形成酰胺或肽键,这些信号与肽聚糖结合,作为细胞壁的主要结构,并促进每个微生物与宿主环境有效地相互作用。这些酶在微生物生理学中起着至关重要的作用,有趣的是,对革兰氏阳性菌的序列分析表明,大约 60%的 Sortase 可以分为六个家族,其中 SrtA 和 SrtC 在各种文献中被广泛研究。Sortase 具有多种功能,包括黏附素、内毒素、血液凝固、免疫逃逸因子和跨微生物细胞壁包膜的营养物质转运体。最近的证据证明,去除 Sortase 基因往往会导致宿主细胞黏附机制的丧失和生物膜的抑制。因此,阻断 Sortase 酶是一个强有力的靶标,由于所有革兰氏阳性菌都存在受体,因此它被称为革兰氏阳性病原体的通用药物靶标。Sortase 酶已被深入研究用于抗感染研究,本综述重点关注 Sortase 将表面蛋白锚定在细胞壁包膜上的机制,并强调其作为药物靶标的重要作用。

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