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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP Ribose Transferases / metabolism*
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Actins / metabolism
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Animals
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Apoptosis
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Endocytosis
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Epithelial Cells / metabolism*
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Epithelial Cells / pathology
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Epithelial Cells / virology*
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HeLa Cells
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Humans
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Intracellular Space / metabolism
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Mice
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Neisseria meningitidis / metabolism*
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Protein Binding
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Protein Transport
Substances
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Actins
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ADP Ribose Transferases
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NarE protein, Neisseria meningitidis
Grants and funding
This work was supported by internal funding by Novartis Vaccines and Diagnostics S.r.l.—a GSK company- and grants from the Italian Association for Cancer Research (AIRC, Milan, Italy; IG10341 and IG14675) and the PON project no. 01/00117. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Novartis Vaccines and Diagnostics S.r.l.—a GSK company- provided support in the form of salaries for authors MV, VZ, LL, MGP, MS, SRP but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.