The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial Cells and Disrupts Epithelial Monolayer Integrity.

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 moie...

Full description

Bibliographic Details
Main Authors: Maria Valeri, Vanessa Zurli, Inmaculada Ayala, Antonino Colanzi, Lucia Lapazio, Daniela Corda, Marco Soriani, Mariagrazia Pizza, Silvia Rossi Paccani
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0127614
id doaj-78b28bc2c470453b8800ca22f26e5ef9
record_format Article
spelling doaj-78b28bc2c470453b8800ca22f26e5ef92021-03-03T20:04:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012761410.1371/journal.pone.0127614The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial Cells and Disrupts Epithelial Monolayer Integrity.Maria ValeriVanessa ZurliInmaculada AyalaAntonino ColanziLucia LapazioDaniela CordaMarco SorianiMariagrazia PizzaSilvia Rossi PaccaniMany 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.https://doi.org/10.1371/journal.pone.0127614
collection DOAJ
language English
format Article
sources DOAJ
author Maria Valeri
Vanessa Zurli
Inmaculada Ayala
Antonino Colanzi
Lucia Lapazio
Daniela Corda
Marco Soriani
Mariagrazia Pizza
Silvia Rossi Paccani
spellingShingle Maria Valeri
Vanessa Zurli
Inmaculada Ayala
Antonino Colanzi
Lucia Lapazio
Daniela Corda
Marco Soriani
Mariagrazia Pizza
Silvia Rossi Paccani
The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial Cells and Disrupts Epithelial Monolayer Integrity.
PLoS ONE
author_facet Maria Valeri
Vanessa Zurli
Inmaculada Ayala
Antonino Colanzi
Lucia Lapazio
Daniela Corda
Marco Soriani
Mariagrazia Pizza
Silvia Rossi Paccani
author_sort Maria Valeri
title The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial Cells and Disrupts Epithelial Monolayer Integrity.
title_short The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial Cells and Disrupts Epithelial Monolayer Integrity.
title_full The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial Cells and Disrupts Epithelial Monolayer Integrity.
title_fullStr The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial Cells and Disrupts Epithelial Monolayer Integrity.
title_full_unstemmed The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial Cells and Disrupts Epithelial Monolayer Integrity.
title_sort neisseria meningitidis adp-ribosyltransferase nare enters human epithelial cells and disrupts epithelial monolayer integrity.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2015-01-01
description 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.
url https://doi.org/10.1371/journal.pone.0127614
work_keys_str_mv AT mariavaleri theneisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT vanessazurli theneisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT inmaculadaayala theneisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT antoninocolanzi theneisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT lucialapazio theneisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT danielacorda theneisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT marcosoriani theneisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT mariagraziapizza theneisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT silviarossipaccani theneisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT mariavaleri neisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT vanessazurli neisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT inmaculadaayala neisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT antoninocolanzi neisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT lucialapazio neisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT danielacorda neisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT marcosoriani neisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT mariagraziapizza neisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
AT silviarossipaccani neisseriameningitidisadpribosyltransferasenareentershumanepithelialcellsanddisruptsepithelialmonolayerintegrity
_version_ 1714824218019889152