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Tracking bacterial effector protein delivery into host cells
Molecular Microbiology ( IF 3.6 ) Pub Date : 2021-07-12 , DOI: 10.1111/mmi.14784
Timothy L Cover 1, 2, 3
Affiliation  

Bacterial Type IV secretion systems (T4SSs) are a functionally heterogeneous group of nanomachines that can deliver substrates into a wide range of target cells. The Helicobacter pylori Cag T4SS has an important role in the pathogenesis of gastric cancer. CagA, the only effector protein known to be secreted by the H. pylori Cag T4SS, enters human gastric cells and causes alterations in intracellular signaling that are linked to cancer pathogenesis. Understanding the molecular mechanisms by which CagA is delivered into gastric cells has been hindered by the lack of robust methods for monitoring this process. A publication in this issue of Molecular Microbiology describes a split luciferase assay for monitoring T4SS-mediated translocation of CagA into host cells. The use of this translocation reporter allowed the quantification of CagA translocation in real-time assays, thereby facilitating the analysis of the kinetics of CagA delivery. This system also allowed the tracking of several types of CagA fusion proteins and confirmed that protein unfolding is important for secretion by the Cag T4SS. This commentary discusses T4SS-dependent delivery of H. pylori CagA into host cells and the use of the split luciferase system for monitoring bacterial protein secretion and delivery into target cells.

中文翻译:

跟踪细菌效应蛋白向宿主细胞的传递

细菌 IV 型分泌系统 (T4SSs) 是一组功能异质的纳米机器,可以将底物输送到广泛的靶细胞中。幽门螺杆菌Cag T4SS在胃癌的发病机制中具有重要作用。CagA 是已知的唯一一种由幽门螺杆菌Cag T4SS 分泌的效应蛋白,它进入人胃细胞并引起与癌症发病机制相关的细胞内信号传导的改变。由于缺乏可靠的方法来监测这一过程,阻碍了了解 CagA 被传递到胃细胞中的分子机制。本期《分子微生物学》上的一篇文章描述了用于监测 T4SS 介导的 CagA 易位到宿主细胞中的分裂荧光素酶测定。使用这种易位报告器可以在实时检测中量化 CagA 易位,从而促进 CagA 传递动力学的分析。该系统还允许跟踪几种类型的 CagA 融合蛋白,并证实蛋白质去折叠对于 Cag T4SS 的分泌很重要。本评论讨论了H. pylori CagA 依赖 T4SS 递送到宿主细胞中,以及使用分裂荧光素酶系统监测细菌蛋白质分泌和递送到靶细胞中。
更新日期:2021-07-12
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