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

Abstract

SummaryDuring 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 (b2GPI), 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 b2GPI and thereby prevent the processing of b2GPI 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, b2GPI-derived antibacterial peptides. Taken together, the data suggest that the interaction between the streptococcal proteins and b2GPI or b2GPI-derived peptides presents a novel mechanism to resist an antibacterial attack by b2GPI-cleavage products.

Highly Selective End-Tagged Antimicrobial Peptides Derived from PRELP

“…Conversely, cationic peptide motifs from proteins not previously considered as AMPs have been shown to exert antimicrobial activities. For example, complement C3 [17], kininogen [18], [19], heparin-binding protein [20], heparin-binding epidermal growth factor and other growth factors [21], matrix proteins such as laminin, fibronectin and proline arginine-rich end leucine-rich repeat protein (PRELP)[22], prions [23], β2-glycoprotein [24], histidine-rich glycoprotein [25], thrombin [26], and tissue factor pathway inhibitor [27], may, either as holoproteins or smaller peptide derivatives or fragments thereof, also exert antimicrobial activities i n vitro , and in several cases, in vivo [18], [19], [25]. In general, these findings are compatible with the observation that consensus heparin-binding peptide sequences (Cardin and Weintraub motifs) XBBBXXBX or XBBXBX (where X represents hydrophobic or uncharged amino acids, and B represents basic amino acids), represented by multiples of the motifs ARKKAAKA or AKKARA [28], are antibacterial [29] and specifically interact with membranes [30].…”

Histidine-rich glycoprotein: the Swiss Army knife of mammalian plasma

“…90 Proteolytic cleavage of HMWK can also generate 2-chain HMWK that inhibits angiogenesis. 91 Furthermore, cleavage of ␤ 2 GPI by plasmin 92 and polymorphonuclear neutrophil-derived proteases 93 has been shown to regulate the ability of ␤ 2 GPI to exhibit antiangiogenic and antibacterial activities. Similarly, cleavage of HRG by plasmin and other proteases has been proposed as a potential mechanism for the generation of antiangiogenic and antimicrobial fragments.…”

Apolipoprotein H, an Acute Phase Protein, a Performing Tool for Ultra-Sensitive Detection and Isolation of Microorganisms from Different Origins

“…Thus, ApoH contributes as a precursor to the human innate immunity. However, it has been hypothesized that some bacteria, including S. pyogenes, may have developed defense mechanisms against the ApoH-derived peptides (Nilsson et al, 2008). Fig.…”

“…11. Mechanisms used by Streptococcus pyogenes AP1 to neutralize the effect of antibacterial peptides derived from ApoH (Nilsson et al, 2008 The first mechanism is the link between the bacterium and the ApoH. Once ApoH is bound to bacteria, proteinases from PMN cannot cleave ApoH and therefore the production of antibacterial ApoH-derived peptides is reduced (Fig.…”

“…M1 protein is a virulence factor, allowing the bacteria to resist phagocytosis. The M1 protein would interact with plasma proteins (fibrinogen, C4b binding protein, H factor) to avoid bacterial lysis (Nilsson et al, 2008).…”