title: Neisseria meningitidis App, a new adhesin with autocatalytic serine protease activity.
abstract: Neisseria meningitidis is a Gram-negative bacterium which colonizes the human upper respiratory tract. Occasionally, it translocates to the bloodstream causing sepsis and from there it can cross the blood-brain barrier and cause meningitis. Many of the molecules, which mediate the interaction of N. meningitidis to host cells, are still unknown. Recently, App (Adhesion and penetration protein) was described as a member of the autotransporter family and a homologue to the Hap (Haemophilus adhesion and penetration) protein of Haemophilus influenzae, a molecule that plays a role in the interaction with human epithelial cells. In this study we expressed app in Escherichia coli in order to analyse the functional properties of the protein. We show that the protein is exported to the E. coli surface, processed by an endogenous serine-protease activity and released in the culture supernatant. Escherichia coli expressing app adhere to Chang epithelial cells, showing that App is able to mediate bacterial adhesion to host cells. The serine protease activity is localized at the amino-terminal domain, whereas the binding domain is in the carboxy-terminal region. The role of App in adhesion was confirmed also in N. meningitidis.
authors.affiliation: IRIS, Chiron S. r.l., via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Serruto
authors.forename: Jeannette
authors.initials: J
authors.lastname: Adu-Bobie
authors.forename: Maria
authors.initials: M
authors.lastname: Scarselli
authors.forename: Daniele
authors.initials: D
authors.lastname: Veggi
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Beatrice
authors.initials: B
authors.lastname: Aricò
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000378:metabolism*; D011485:Protein Binding; D016415:Sequence Alignment; D012694:Serine / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
chemical_list: C450760:APP protein, Neisseria meningitidis; D001425:Bacterial Outer Membrane Proteins; D012694:Serine; D012697:Serine Endopeptidases