TY - JOUR A1 - Zakrzewicz, Dariusz A1 - Bergmann, Simone A1 - Didiasova, Miroslava A1 - Giaimo, Benedetto Daniele A1 - Borggrefe, Tilman A1 - Mieth, Maren A1 - Hocke, Andreas Christian A1 - Lochnit, Günter A1 - Schäfer, Liliana A1 - Hammerschmidt, Sven A1 - Preissner, Klaus T. A1 - Wygrecka, Malgorzata T1 - Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to endothelial and epithelial cells T2 - Scientific reports N2 - 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. KW - Bacterial infection KW - Bacterial pathogenesis Y1 - 2016 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46500 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-465005 SN - 2045-2322 N1 - 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/ VL - 6 IS - Art. 37758 SP - 1 EP - 13 PB - Macmillan Publishers Limited, part of Springer Nature CY - [London] ER -