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

Sci Rep. 2016 Nov 28;6:37758. doi: 10.1038/srep37758.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Amino Acid Motifs
  • Animals
  • Bacterial Adhesion / drug effects*
  • Binding Sites
  • Cattle
  • DNA / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / microbiology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / microbiology*
  • Extracellular Space / metabolism*
  • 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
  • RNA / pharmacology*
  • Ribonuclease, Pancreatic / metabolism
  • Streptococcus pneumoniae / cytology*
  • Streptococcus pneumoniae / drug effects

Substances

  • Nucleotides
  • RNA
  • DNA
  • Ribonuclease, Pancreatic
  • Phosphopyruvate Hydratase
  • Lysine
  • Glycine