title: The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial Cells and Disrupts Epithelial Monolayer Integrity.
abstract: Many pathogenic bacteria utilize ADP-ribosylating toxins to modify and impair essential functions of eukaryotic cells. It has been previously reported that Neisseria meningitidis possesses an ADP-ribosyltransferase enzyme, NarE, retaining the capacity to hydrolyse NAD and to transfer ADP-ribose moiety to arginine residues in target acceptor proteins. Here we show that upon internalization into human epithelial cells, NarE gains access to the cytoplasm and, through its ADP-ribosylating activity, targets host cell proteins. Notably, we observed that these events trigger the disruption of the epithelial monolayer integrity and the activation of the apoptotic pathway. Overall, our findings provide, for the first time, evidence for a biological activity of NarE on host cells, suggesting its possible involvement in Neisseria pathogenesis.
authors.affiliation: Vaccines & Diagnostics s.r.l.-a GSK company- Via Fiorentina 1, Siena, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Valeri
authors.affiliation: Vaccines & Diagnostics s.r.l.-a GSK company- Via Fiorentina 1, Siena, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Zurli
authors.affiliation: Institute of Protein Biochemistry, National Research Council, Via P. Castellino 111, Naples, Italy.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ayala
authors.affiliation: Institute of Protein Biochemistry, National Research Council, Via P. Castellino 111, Naples, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Colanzi
authors.affiliation: Vaccines & Diagnostics s.r.l.-a GSK company- Via Fiorentina 1, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Lapazio
authors.affiliation: Institute of Protein Biochemistry, National Research Council, Via P. Castellino 111, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Corda
authors.affiliation: Vaccines & Diagnostics s.r.l.-a GSK company- Via Fiorentina 1, Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Soriani
authors.affiliation: Vaccines & Diagnostics s.r.l.-a GSK company- Via Fiorentina 1, Siena, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.affiliation: Vaccines & Diagnostics s.r.l.-a GSK company- Via Fiorentina 1, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi Paccani
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D009345:Neisseria meningitidis / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D000199:Actins; D036002:ADP Ribose Transferases; C480854:NarE protein, Neisseria meningitidis