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

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 (β2GPI), 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 β2GPI and thereby prevent the processing of β 2GPI 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, β2GPI-derived antibacterial peptides. Taken together, the data suggest that the interaction between the streptococcal proteins and β2GPI or β2GPI-derived peptides presents a novel mechanism to resist an antibacterial attack by β2GPI-cleavage products. © 2007 The Authors.