Helicobacter pylori outer membrane protein HopQ identified as a novel T4SS-associated virulence factor.

ABSTRACT: Helicobacter pylori is a bacterial pathogen that colonizes the gastric niche of ??50% of the human population worldwide and is known to cause peptic ulceration and gastric cancer. Pathology of infection strongly depends on a cag pathogenicity island (cagPAI)-encoded type IV secretion system (T4SS). Here, we aimed to identify as yet unknown bacterial factors involved in cagPAI effector function and performed a large-scale screen of an H.?pylori transposon mutant library using activation of the pro-inflammatory transcription factor NF-?B in human gastric epithelial cells as a measure of T4SS function. Analysis of ??3000 H.?pylori mutants revealed three non-cagPAI genes that affected NF-?B nuclear translocation. Of these, the outer membrane protein HopQ from H.?pylori strain P12 was essential for CagA translocation and for CagA-mediated host cell responses such as formation of the hummingbird phenotype and cell scattering. Besides that, deletion of hopQ reduced T4SS-dependent activation of NF-?B, induction of MAPK signalling and secretion of interleukin 8 (IL-8) in the host cells, but did not affect motility or the quantity of bacteria attached to host cells. Hence, we identified HopQ as a non-cagPAI-encoded cofactor of T4SS function.

SUBMITTER: Belogolova E 

PROVIDER: S-EPMC3797234 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature