Domain 4 of pneumolysin from Streptococcus pneumoniae is a multifunctional domain contributing TLR4 activating and hemolytic activity

Biochem Biophys Res Commun. 2019 Oct 1;517(4):596-602. doi: 10.1016/j.bbrc.2019.07.063. Epub 2019 Aug 5.

Abstract

The pneumolysin (Ply) protein of Streptococcus pneumoniae is composed of four domains and possesses several different but related activities. In this study, recombinant Ply and two truncated forms, Ply domain 1-3 and Ply domain 4 (rPly4), were expressed and characterized regarding their participation in apoptosis, the stimulation of cytokine production, hemolytic activity and virulence. rPly4 activated murine bone marrow-derived dendritic cells in a Toll-like receptor (TLR) 4-dependent manner. The rPly4 alone was able to produce hemolytic activity at high concertation and penetrate the lipid bilayer. We further demonstrated that domain 4 of Ply involved in the virulence of the bacteria in mouse model. In the absence of apoptotic activity, the virulence level caused by rPly4 was similar to that of full length Ply. Our data suggested that domain 4 of Ply alone with TLR4 agonist and hemolytic activity may play roles in virulence of Streptococcus pneumoniae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / pharmacology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Female
  • Hemolysis*
  • Humans
  • Mice, Inbred ICR
  • Protein Domains
  • Recombinant Proteins / pharmacology
  • Streptococcus pneumoniae / pathogenicity
  • Streptolysins / chemistry*
  • Streptolysins / metabolism*
  • Streptolysins / pharmacology
  • Structure-Activity Relationship
  • Toll-Like Receptor 4 / metabolism*
  • Virulence / drug effects

Substances

  • Bacterial Proteins
  • Recombinant Proteins
  • Streptolysins
  • Toll-Like Receptor 4
  • plY protein, Streptococcus pneumoniae