title: Coiled coil rich proteins (Ccrp) influence molecular pathogenicity of Helicobacter pylori.
abstract: Pathogenicity of the human pathogen Helicobacter pylori relies on its capacity to adapt to a hostile environment and to escape the host response. Although there have been great advances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowledge of its contribution to virulence. In this study we have explored the influence of coiled coil rich proteins (Ccrp) cytoskeletal elements on pathogenicity factors of H. pylori. Deletion of any of the ccrp resulted in a strongly decreased activity of the main pathogenicity factor urease. We further investigated their role using in vitro co-culture experiments with the human gastric adenocarcinoma cell line AGS modeling H. pylori - host cell interactions. Intriguingly, host cell showed only a weak "scattering/hummingbird" phenotype, in which host cells are transformed from a uniform polygonal shape into a severely elongated state characterized by the formation of needle-like projections, after co-incubation with any ccrp deletion mutant. Furthermore, co-incubation with the ccrp59 mutant resulted in reduced type IV secretion system associated activities, e.g. IL-8 production and CagA translocation/phosphorylation. Thus, in addition to their role in maintaining the helical cell shape of H. pylori Ccrp proteins influence many cellular processes and are thereby crucial for the virulence of this human pathogen.
authors.affiliation: Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Hospital Freiburg, Hermann-Herder Straße 11, 79104 Freiburg, Germany; Department of Microbiology, Faculty for Biology, University of Freiburg, Schaenzle Straße 1, 79104 Freiburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schätzle
authors.affiliation: LOEWE Center for Synthetic Microbiology, Hans-Meerwein Straße 35032 Marburg, Germany.
authors.forename: Mara
authors.initials: M
authors.lastname: Specht
authors.affiliation: Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Hospital Freiburg, Hermann-Herder Straße 11, 79104 Freiburg, Germany; Department of Microbiology, Faculty for Biology, University of Freiburg, Schaenzle Straße 1, 79104 Freiburg, Germany; LOEWE Center for Synthetic Microbiology, Hans-Meerwein Straße 35032 Marburg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Waidner
mesh_terms: D000942:Antigens, Bacterial / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D005798:Genes, Bacterial; D016481:Helicobacter Infections / Q000209:etiology / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D009154:Mutation; D010641:Phenotype; D000069319:Type IV Secretion Systems / Q000235:genetics / Q000502:physiology; D014510:Urease / Q000378:metabolism; D014774:Virulence / Q000235:genetics / Q000502:physiology; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C508606:CXCL8 protein, human; D016209:Interleukin-8; D000069319:Type IV Secretion Systems; D037521:Virulence Factors; C080866:cagA protein, Helicobacter pylori; D014510:Urease
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