title: Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to endothelial and epithelial cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Zakrzewicz
authors.affiliation: Department of Medical Microbiology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Bergmann
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Didiasova
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.
authors.forename: Benedetto Daniele
authors.initials: BD
authors.lastname: Giaimo
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Borggrefe
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-University Medicine Berlin, Chariteplatz 1, 10117 Berlin, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Mieth
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-University Medicine Berlin, Chariteplatz 1, 10117 Berlin, Germany.
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Hocke
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.
authors.forename: Guenter
authors.initials: G
authors.lastname: Lochnit
authors.affiliation: Institute of Pharmacology and Toxicology, Goethe University School of Medicine, University Hospital, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Liliana
authors.initials: L
authors.lastname: Schaefer
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt Universität Greifswald, Friedrich-Ludwig-Jahn-Strasse 15a, 17489 Greifswald, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.|German Centre for Lung Research, Giessen, Germany.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Wygrecka
mesh_terms: D000072283:A549 Cells; D020816:Amino Acid Motifs; D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects*; D001665:Binding Sites; D002417:Cattle; D004247:DNA / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000382:microbiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology*; D005110:Extracellular Space / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000473:pathology; D008239:Lysine / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009711:Nucleotides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011008:Pneumococcal Infections / Q000382:microbiology / Q000473:pathology; D012313:RNA / Q000494:pharmacology*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000166:cytology* / Q000187:drug effects
chemical_list: D009711:Nucleotides; D012313:RNA; D004247:DNA; D012259:Ribonuclease, Pancreatic; D010751:Phosphopyruvate Hydratase; D008239:Lysine; D005998:Glycine