Helicobacter pylori-Derived Outer Membrane Vesicles (OMVs): Role in Bacterial Pathogenesis?

Abstract

Persistent infections with the human pathogen Helicobacter pylori (H. pylori) have been closely associated with the induction and progression of a wide range of gastric disorders, including acute and chronic gastritis, ulceration in the stomach and duodenum, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. The pathogenesis of H. pylori is determined by a complicated network of manifold mechanisms of pathogen-host interactions, which involves a coordinated interplay of H. pylori pathogenicity and virulence factors with host cells. While these molecular and cellular mechanisms have been intensively investigated to date, the knowledge about outer membrane vesicles (OMVs) derived from H. pylori and their implication in bacterial pathogenesis is not well developed. In this review, we summarize the current knowledge on H. pylori-derived OMVs.

Keywords: CagA; Helicobacter pylori; HtrA; OMV; VacA; outer membrane vesicles; urease.

Figure 1

Virulence factors detected in H. pylori-derived OMVs. Identified virulence factors of H. pylori by mass spectroscopy [38,39,40,41,42,45] and their role in bacterial pathogenesis.

Figure 2

Model of OMV interaction with host cells. H. pylori releases OMVs, which attach to the cell surface of gastric epithelial cells. Clathrin-dependent and -independent uptake of OMVs could occur via phagocytosis leading to the formation of endosomes and/or fusion of the bacterial OMV membrane with the host´s membrane. The fate of internalized OMVs is unclear, but the release of OMVs at the basolateral membrane (transcytosis) or into the cytoplasm was hypothesized. OMV-delivered virulence factors might be released into the cytosol where they can interfere with host cell signaling leading to inflammation and carcinogenesis (left panel). Technical applications of H. pylori OMVs as nanocarriers for drugs or proteins (right panel).

Figure 3

Localization of CagA in H. pylori. CagA (green) was detected using an anti-CagA antibody and analyzed by STED microscopy. Bacterial DNA was stained using DAPI (blue). Bar, 1 µM.