鲍曼不动杆菌VI型分泌系统功能蛋白的研究及应用新进展

Advances in functional proteins of type VI secretion system of Acinetobacter baumannii

摘要:

细菌VI型分泌系统（type VI secretion system，T6SS）作为一个动态多蛋白复合体，各元件之间分工明确，转运各种效应蛋白作用于竞争细菌获得自我生长优势。鲍曼不动杆菌（Acinetobacter baumannii，Ab）通过T6SS介导细菌在微生物群落中的竞争能力，影响其耐药进化、宿主侵袭感染等过程。其中，缬氨酸-甘氨酸-精氨酸G蛋白三聚体（valine-glycine repeat protein G，VgrG）、脯氨酸-丙氨酸-丙氨酸-精氨酸重复序列蛋白（proline-alanine-alanine-arginine，PAAR）、溶血素共调节蛋白（hemolysin-coregulated protein，Hcp）和效应-免疫（effector-immunity，E-I）对发挥着关键作用。有关T6SS的研究总结虽然很多，但是鲜有文章系统概述其临床应用前景，因为这对T6SS功能蛋白的鉴定、特性、转运机制等基础研究的进展提出了挑战。本文通过综述鲍曼不动杆菌中T6SS的分布、主要功能蛋白的特性及转运机制的研究进展，结合T6SS的应用案例，提供其应用的可行性证据。以期进一步推动鲍曼不动杆菌VI型分泌系统基因和功能的研究，为开发新型抗感染疫苗、筛选合适的靶点抑制剂及生产工程化药物递送工具提供新的思路。

关键词:鲍曼不动杆菌;VI型分泌系统;缬氨酸-甘氨酸-精氨酸G蛋白三聚体;脯氨酸-丙氨酸-丙氨酸-精氨酸重复序列蛋白;溶血素共调节蛋白;效应-免疫对

Abstract:

The type VI secretion system (T6SS) as a dynamic multi-protein complex has a clear division of labor among its components, transporting effector proteins to compete for bacterial growth. Studies have shown that T6SS mediates the competitiveness of Acinetobacter baumannii in the microbial community and affects the drug resistance evolution and invasion in the host. Particularly, the valine-glycine repeat protein G (VgrG), the proline-alanine- alanine-arginine (PAAR), the hemolysin-coregulated protein (Hcp), and the effector-immunity (E-I) pair play a key role. Although T6SS has been extensively studied, there are few articles about its clinical application prospects, as this poses challenges to the identification, characterization, transport mechanism revealing, and other basic research on their functional proteins. We reviewed the research progress in the distribution, functional protein characteristics, and transport mechanism of T6SS in A. baumannii and provided evidence for its application based on the application cases of T6SS. This review aims to promote the research on the genes and functions of T6SS in A. baumannii and provide new targets and ideas for developing new anti-infective vaccines, screening suitable inhibitors, and producing engineered drug delivery tools.

Key words:Acinetobacter baumannii;type VI secretion system;valine-glycine repeat protein G;proline-alanine-alanine-arginine;hemolysin-coregulated protein;effector-immunity pair