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Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to endothelial and epithelial cells.
- Source :
-
Scientific reports [Sci Rep] 2016 Nov 28; Vol. 6, pp. 37758. Date of Electronic Publication: 2016 Nov 28. - Publication Year :
- 2016
-
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.
- Subjects :
- A549 Cells
Amino Acid Motifs
Animals
Binding Sites
Cattle
DNA metabolism
Endothelial Cells drug effects
Epithelial Cells drug effects
Glycine metabolism
Humans
Lung pathology
Lysine metabolism
Mutation genetics
Nucleotides metabolism
Phosphopyruvate Hydratase chemistry
Phosphopyruvate Hydratase genetics
Phosphopyruvate Hydratase metabolism
Pneumococcal Infections microbiology
Pneumococcal Infections pathology
Ribonuclease, Pancreatic metabolism
Streptococcus pneumoniae drug effects
Bacterial Adhesion drug effects
Endothelial Cells microbiology
Epithelial Cells microbiology
Extracellular Space metabolism
RNA pharmacology
Streptococcus pneumoniae cytology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 27892961
- Full Text :
- https://doi.org/10.1038/srep37758