Streptococcus pneumoniae endopeptidase O (PepO): a multifunctional plasminogen and fibronectin binding protein, facilitating evasion of innate immunity and invasion of host cells.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Streptococcus pneumoniae infections remain a major cause of morbidity and mortality worldwide. Therefore a detailed understanding and characterization of the mechanism of host cell colonization and dissemination is critical in order to gain control over this versatile pathogen. Here we identified a novel 72 kDa pneumococcal protein endopeptidase O (PepO), as a plasminogen and fibronectin binding protein. Using a collection of clinical isolates, representing different serotypes, we found PepO to be ubiquitously present both at the gene and at the protein level. In addition, PepO protein was secreted in a growth-phase dependent manner to the culture supernatants of the pneumococcal isolates. Recombinant PepO bound human plasminogen and fibronectin in a dose-dependent manner and plasminogen did not compete with fibronectin for binding PepO. PepO bound plasminogen via lysine residues and the interaction was influenced by ionic strength. Moreover, upon activation of PepO bound plasminogen by urokinase-type plasminogen activator, generated plasmin cleaved complement protein C3b thus assisting in complement control. Furthermore, direct binding assays demonstrated the interaction of PepO with epithelial and endothelial cells that in turn blocked pneumococcal adherence. Moreover, a pepO-mutant strain showed impaired adherence to and invasion of host cells compared to their isogenic wild-type strains. Taken together, the results demonstrated that PepO is ubiquitously expressed plasminogen and fibronectin binding protein, which plays role in pneumococcal invasion of host cells and aids in immune evasion.

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Annan medicinsk grundvetenskap
  • Mikrobiologi inom det medicinska området
Originalspråkengelska
Sidor (från-till)6849-6863
TidskriftJournal of Biological Chemistry
Volym288
Utgåva nummer10
StatusPublished - 2013
PublikationskategoriForskning
Peer review utfördJa

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