title: Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion.
abstract: Mammalian and prokaryotic high-temperature requirement A (HtrA) proteins are chaperones and serine proteases with important roles in protein quality control. Here, we describe an entirely new function of HtrA and identify it as a new secreted virulence factor from Helicobacter pylori, which cleaves the ectodomain of the cell-adhesion protein E-cadherin. E-cadherin shedding disrupts epithelial barrier functions allowing H. pylori designed to access the intercellular space. We then designed a small-molecule inhibitor that efficiently blocks HtrA activity, E-cadherin cleavage and intercellular entry of H. pylori.
authors.affiliation: Junior Research Group, Paul-Ehrlich Institute, Langen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hoy
authors.forename: Martin
authors.initials: M
authors.lastname: Löwer
authors.forename: Christiane
authors.initials: C
authors.lastname: Weydig
authors.forename: Gert
authors.initials: G
authors.lastname: Carra
authors.forename: Nicole
authors.initials: N
authors.lastname: Tegtmeyer
authors.forename: Tim
authors.initials: T
authors.lastname: Geppert
authors.forename: Peter
authors.initials: P
authors.lastname: Schröder
authors.forename: Norbert
authors.initials: N
authors.lastname: Sewald
authors.forename: Steffen
authors.initials: S
authors.lastname: Backert
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
authors.forename: Silja
authors.initials: S
authors.lastname: Wessler
mesh_terms: D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D015820:Cadherins; D015815:Cell Adhesion Molecules; D037521:Virulence Factors
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