基于蛋白质跨外膜自转运系统的细菌细胞表面蛋白展示技术研究进展

Trend of bacterial cell surface display: the autodisplay technology

摘要:

革兰氏阴性菌Ⅴ型分泌系统是细菌病原蛋白分泌的主要途径之一，可分为Ⅴa–Ⅴe 5个亚型，其中Ⅴa型（即经典的单体自转运蛋白）是细菌毒力和黏附因子向细胞外分泌的重要工具，其在内膜Sec易位子和外膜BAM蛋白复合体的协助下，通过2个连续的跨膜步骤介导蛋白质穿过阴性菌的内外膜。据信Ⅴa型是目前已知蛋白质跨膜转运时最简单的分泌途径，故该蛋白质分泌系统作为一种生物工程手段被认为是进行外源蛋白细菌细胞表面展示的理想系统。本文概括了目前已知的自转运蛋白的种类、结构域组成及其可能的分泌机理，总结基于自转运蛋白构建细菌细胞表面展示系统的生物工程应用，特别是其在疫苗研发领域的最新研究进展，并探讨了其在病原体检测方面的潜在应用，以期深入拓展该分泌系统在生物工程方面的应用。

Abstract:

Type V secretion system, one of the key pathways employed by Gram-negative bacteria to secrete virulence factors, is classified into five subtypes (Va-Ve). Among them, type Va (also known as the classical monomeric autotransporters) is extensively used to export virulence and adhesion factors to the bacterial cell surface or into their surroundings, a process combining the passage across the inner and the outer membrane in two consecutive steps that are facilitated by the Sec translocon and the BAM (β-barrel assembly machinery) complex, respectively. It is believed that type Va is the simplest secretion system for the translocation of proteins across membranes, which is therefore considered as an ideal biotechnological tool to display recombinant proteins on bacterial cell surface. In this review, we first summarized the subtypes, structural domains, and possible secretion mechanisms of autotransporters to enhance the understanding of them as a biotechnological tool for various surface display purposes, particularly vaccine development. Then, we explored the potential application of autodisplay in pathogen detection to further expand its application as a biotechnological tool.