title: Neisseria meningitidis NadA is a new invasin which promotes bacterial adhesion to and penetration into human epithelial cells.
abstract: Neisseria meningitidis is a human pathogen, which is a major cause of sepsis and meningitis. The bacterium colonizes the upper respiratory tract of approximately 10% of humans where it lives as a commensal. On rare occasions, it crosses the epithelium and reaches the bloodstream causing sepsis. From the bloodstream it translocates the blood-brain barrier, causing meningitis. Although all strains have the potential to cause disease, a subset of them, which belongs to hypervirulent lineages, causes disease more frequently than others. Recently, we described NadA, a novel antigen of N. meningitidis, present in three of the four known hypervirulent lineages. Here we show that NadA is a novel bacterial invasin which, when expressed on the surface of Escherichia coli, promotes adhesion to and invasion into Chang epithelial cells. Deletion of the N-terminal globular domain of recombinant NadA or pronase treatment of human cells abrogated the adhesive phenotype. A hypervirulent strain of N. meningitidis where the nad A gene was inactivated had a reduced ability to adhere to and invade into epithelial cells in vitro. NadA is likely to improve the fitness of N. meningitidis contributing to the increased virulence of strains that belong to the hypervirulent lineages.
authors.affiliation: Chiron Vaccines, via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Capecchi
authors.forename: Jeannette
authors.initials: J
authors.lastname: Adu-Bobie
authors.forename: Federica
authors.initials: F
authors.lastname: Di Marcello
authors.forename: Laura
authors.initials: L
authors.lastname: Ciucchi
authors.forename: Vega
authors.initials: V
authors.lastname: Masignani
authors.forename: Annarita
authors.initials: A
authors.lastname: Taddei
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Beatrice
authors.initials: B
authors.lastname: Aricò
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001422:Bacterial Adhesion; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000382:microbiology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009345:Neisseria meningitidis / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; C501982:NadA protein, Neisseria meningitidis