title: The Helicobacter pylori Autotransporter ImaA Tempers the Bacterium's Interaction with α5β1 Integrin.
abstract: The human pathogen Helicobacter pylori uses the host receptor α5β1integrin to trigger inflammation in host cells via its cag pathogenicity island (cag PAI) type IV secretion system (T4SS). Here, we report that the H. pylori ImaA protein (HP0289) decreases the action of the cag PAI T4SS via tempering the bacterium's interaction with α5β1integrin. Previously, imaA-null mutants were found to induce an elevated inflammatory response that was dependent on the cag PAI T4SS; here we extend those findings to show that the elevated response is independent of the CagA effector protein. To understand how ImaA could be affecting cag PAI T4SS activity at the host cell interface, we utilized the Phyre structural threading program and found that ImaA has a region with remote homology to bacterial integrin-binding proteins. This region was required for ImaA function. Unexpectedly, we observed that imaA mutants bound higher levels of α5β1integrin than wild-type H. pylori, an outcome that required the predicted integrin-binding homology region of ImaA. Lastly, we report that ImaA directly affected the amount of host cell β1 integrin but not other cellular integrins. Our results thus suggest a model in which H. pylori employs ImaA to regulate interactions between integrin and the T4SS and thus alter the host inflammatory strength.
authors: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, California, USA.
authors: William E
authors: WE
authors: Sause
authors: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, California, USA.
authors: Daniela
authors: D
authors: Keilberg
authors: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, California, USA.
authors: Soufiane
authors: S
authors: Aboulhouda
authors: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, California, USA Ottemann@ucsc.edu.
authors: Karen M
authors: http://orcid.org/0000-0001-6265-7401
authors: KM
authors: Ottemann
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D044404:Genomic Islands / Q000235:genetics; D016481:Helicobacter Infections / Q000235:genetics* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D000069319:Type IV Secretion Systems / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D039081:Integrin alpha5beta1; D000069319:Type IV Secretion Systems
keywords: autotransporter proteins; inflammation; pathogenesis; secretion systems; virulence factors