title: 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-κB 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-κB 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-κB, 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.
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, D-10117, Berlin, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Belogolova
authors.forename: Bianca
authors.initials: B
authors.lastname: Bauer
authors.forename: Malvika
authors.initials: M
authors.lastname: Pompaiah
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asakura
authors.forename: Volker
authors.initials: V
authors.lastname: Brinkman
authors.forename: Claudia
authors.initials: C
authors.lastname: Ertl
authors.forename: Sina
authors.initials: S
authors.lastname: Bartfeld
authors.forename: Taras Y
authors.initials: TY
authors.lastname: Nechitaylo
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Machuy
authors.forename: Nina
authors.initials: N
authors.lastname: Salama
authors.forename: Yuri
authors.initials: Y
authors.lastname: Churin
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Meyer
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D002460:Cell Line; D004251:DNA Transposable Elements; D004847:Epithelial Cells / Q000382:microbiology; D017353:Gene Deletion; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016328:NF-kappa B / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D058947:Bacterial Secretion Systems; D004251:DNA Transposable Elements; D016209:Interleukin-8; D016328:NF-kappa B; D037521:Virulence Factors; D020929:Mitogen-Activated Protein Kinase Kinases