title: The C2 fragment from Neisseria meningitidis antigen NHBA increases endothelial permeability by destabilizing adherens junctions.
abstract: Neisseria meningitidis is a human pathogen that can cause fatal sepsis and meningitis once it reaches the blood stream and the nervous system. Here we demonstrate that a fragment, released upon proteolysis of the surface-exposed protein Neisserial Heparin Binding Antigen (NHBA), by the bacterial protease NalP, alters the endothelial permeability by inducing the internalization of the adherens junction protein VE-cadherin. We found that C2 rapidly accumulates in mitochondria where it induces the production of reactive oxygen species: the latter are required for the phosphorylation of the junctional protein and for its internalization that, in turn, is responsible for the endothelial leakage. Our data support the notion that the NHBA-derived fragment C2 might contribute to the extensive vascular leakage typically associated with meningococcal sepsis.
authors.affiliation: Venetian Institute of Molecular Medicine, Padua, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Casellato
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi Paccani
authors.forename: Riccardo
authors.initials: R
authors.lastname: Barrile
authors.forename: Fleur
authors.initials: F
authors.lastname: Bossi
authors.forename: Laura
authors.initials: L
authors.lastname: Ciucchi
authors.forename: Gaia
authors.initials: G
authors.lastname: Codolo
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Beatrice
authors.initials: B
authors.lastname: Aricò
authors.forename: Marina
authors.initials: M
authors.lastname: de Bernard
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects*; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D009345:Neisseria meningitidis / Q000502:physiology*; D010539:Permeability / Q000187:drug effects*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D037521:Virulence Factors