The antibacterial activity of peptides derived from human beta-2 glycoprotein I is inhibited by protein H and M1 protein from Streptococcus pyogenes

Mol Microbiol. 2008 Feb;67(3):482-92. doi: 10.1111/j.1365-2958.2007.05974.x. Epub 2007 Dec 18.

Abstract

During the last years, the importance of antibacterial peptides has attracted considerable attention. We report here that peptides derived from the fifth domain of beta-2 glycoprotein I (beta(2)GPI), a human heparin binding plasma protein, have antibacterial activities against Gram-positive and Gram-negative bacteria. Streptococcus pyogenes, an important human pathogen that can survive and grow in human blood, has developed mechanisms to escape the attack by these peptides. Thus, protein H and M1 protein, two surface proteins of the highly pathogenic S. pyogenes AP1 strain, bind full-length beta(2)GPI and thereby prevent the processing of beta(2)GPI by proteases from polymorphonuclear neutrophils (PMNs) into antibacterial peptides. In addition, protein H and M1 protein, released from the bacterial cell wall by PMN-derived proteases, bind to, and inhibit the activity of, beta(2)GPI-derived antibacterial peptides. Taken together, the data suggest that the interaction between the streptococcal proteins and beta(2)GPI or beta(2)GPI-derived peptides presents a novel mechanism to resist an antibacterial attack by beta(2)GPI-cleavage products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / antagonists & inhibitors*
  • Anti-Bacterial Agents / pharmacology*
  • Antigens, Bacterial / metabolism*
  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Escherichia coli / drug effects
  • Escherichia coli / ultrastructure
  • Humans
  • Membrane Proteins / metabolism*
  • Microbial Viability
  • Microscopy, Electron, Transmission
  • Microscopy, Immunoelectron
  • Models, Biological
  • Neutrophils / enzymology
  • Neutrophils / immunology
  • Protein Binding
  • Staphylococcus aureus / drug effects
  • Streptococcus pyogenes / immunology
  • Streptococcus pyogenes / metabolism*
  • Streptococcus pyogenes / ultrastructure
  • beta 2-Glycoprotein I / antagonists & inhibitors*
  • beta 2-Glycoprotein I / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Carrier Proteins
  • Membrane Proteins
  • beta 2-Glycoprotein I
  • protein H, Streptococcus
  • streptococcal M protein