Tracking bacterial effector protein delivery into host cells

Abstract

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.

Investigating the Molecular Mechanisms Underlying Early Response to Inflammation and Helicobacter pylori Infection in Human Gastric Epithelial Cells

“…It is encoded by the Cag pathogenicity island and is strongly associated with increased risk of developing gastric adenocarcinoma in infected subjects [6]. The pathogenetic role of T4SS in gastric cancer is linked to the fact that it mediates the translocation of the virulence factor CagA, the only effector protein known to be secreted by the H. pylori Cag T4SS, into host cells [7]. Structural component of the Cag T4SS, such as CagL, have been implicated not only in CagA release, but also in direct inflammatory signals [8].…”