Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to endothelial and epithelial cells

  • Streptococcus pneumoniae is the most frequent cause of community-acquired pneumonia. The infection process involves bacterial cell surface receptors, which interact with host extracellular matrix components to facilitate colonization and dissemination of bacteria. Here, we investigated the role of host-derived extracellular RNA (eRNA) in the process of pneumococcal alveolar epithelial cell infection. Our study demonstrates that eRNA dose-dependently increased S. pneumoniae invasion of alveolar epithelial cells. Extracellular enolase (Eno), a plasminogen (Plg) receptor, was identified as a novel eRNA-binding protein on S. pneumoniae surface, and six Eno eRNA-binding sites including a C-terminal 15 amino acid motif containing lysine residue 434 were characterized. Although the substitution of lysine 434 for glycine (K434G) markedly diminished the binding of eRNA to Eno, the adherence to and internalization into alveolar epithelial cells of S. pneumoniae strain carrying the C-terminal lysine deletion and the mutation of internal Plg-binding motif were only marginally impaired. Accordingly, using a mass spectrometric approach, we identified seven novel eRNA-binding proteins in pneumococcal cell wall. Given the high number of eRNA-interacting proteins on pneumococci, treatment with RNase1 completely inhibited eRNA-mediated pneumococcal alveolar epithelial cell infection. Our data support further efforts to employ RNAse1 as an antimicrobial agent to combat pneumococcal infectious diseases.

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Author:Dariusz Zakrzewicz, Simone Bergmann, Miroslava Didiasova, Benedetto Daniele Giaimo, Tilman Borggrefe, Maren Mieth, Andreas Christian Hocke, Günter Lochnit, Liliana Schäfer, Sven Hammerschmidt, Klaus T. Preissner, Malgorzata Wygrecka
URN:urn:nbn:de:hebis:30:3-465005
DOI:https://doi.org/10.1038/srep37758
ISSN:2045-2322
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/27892961
Parent Title (English):Scientific reports
Publisher:Macmillan Publishers Limited, part of Springer Nature
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2016
Date of first Publication:2016/11/28
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/05/29
Tag:Bacterial infection; Bacterial pathogenesis
Volume:6
Issue:Art. 37758
Page Number:13
First Page:1
Last Page:13
Note:
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
HeBIS-PPN:450868133
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0