Common protective antigens of group A streptococcal M proteins masked by fibrinogen.

Abstract

The surface M protein of group A streptococci is the principal virulence factor of these organisms. Streptococci lacking M protein are efficiently opsonized by the alternate complement pathway (1, 2) and in consequence are rapidly ingested and killed by host leukocytes. Streptococci possessing surface M protein are neither opsonized nor ingested unless antibody to the M protein is present (3). Two hypotheses, which are not mutually exclusive, have been advanced to explain the antiphagocytic properties of M protein: it may be toxic to the phagocyte in some way; or it may prevent opsonization of the streptococcal cells. The first possibility has not been investigated in detail. Crude, hot-acid extracts of M protein are toxic to polymorphonuclear leukocytes, but this appears to be due to the formation of antigen-antibody complexes involving non-type-specific antigens, rather than to a direct toxic effect of the M protein (4). M protein could nonetheless be toxic in the high concentrations prevailing at the surface of a streptococcal cell at its point of attachment to a phagocyte. Recently, Manjula and Fischetti (5) have speculated that M protein, which has certain structural homologies to a-tropomyosin, might disable the phagocyte by interfering with its contractile proteins.The second possibility--that M protein interferes with opsonization--has extensive experimental support. When suspended in fresh serum, streptococci lacking M protein are opsonized by complement via the alternate pathway, which must be intact for phagocytosis to occur (2). Streptococci possessing M protein activate this pathway less efficiently (1, 6). Jacks-Weis and her colleagues (6) noted that although M-positive streptococcal cells did activate complement and bind it (C3) on their surface, the bound C3 was distributed unevenly as shown by immunofluorescence microscopy. They suggested that this patchiness prevented the smooth operation of the "zipper" mechanism of internalization proposed by Griffin et al. (7).In a previous report, we showed that virulent M-rich streptococci, although partially resistant to opsonization when suspended in nonimmune human serum, were completely resistant when suspended in plasma (8). The opsonizationinhibiting activity of plasma was found to reside in fibrinogen: purified fibrinogen

Pathogenesis of Group A Streptococcal Infections

“…The antiphagocytic behavior of group A streptococci is also mediated by the binding of fibrinogen to the surface of M protein (555)(556)(557). Fibrinogen binding to the surface of group A streptococci blocks the activation of complement via the alternate pathway and greatly reduces the amount of C3b bound to streptococci, which therefore reduces phagocytosis by polymorphonuclear leukocytes (247).…”

Group A Streptococcus Expresses a Trio of Surface Proteins Containing Protective Epitopes

“…Virulent GAS multiply in nonimmune human blood because the M protein specifically binds numerous plasma proteins that block or interfere with the activation and deposition of complement (15). Antibodies against the N-terminal regions of the M protein are opsonic and are able to bind to the M epitopes that extend beyond the layer of human plasma proteins covering the cell surface (18). In the current study, we have shown that serotype M65 GAS expressed three distinct cell wall proteins that contained bactericidal epitopes.…”

“…2). In order to mimic the potential in vivo conditions, antibody binding assays were performed in the presence of human plasma, which contains multiple proteins that bind to the bacterial surface (15)(16)(17) that can alter the binding of functional antibodies (18). The M, Mrp, and Spa peptide antisera each reacted with the surface of M65 streptococci in a semicircular pattern at the pole of each coccus, a location that represents the mature cell wall with fully inserted integral proteins (Fig.…”

Surface-associated properties of Streptococcus milleri group strains and their potential relation to pathogenesis

“…It has been proposed that the ability of strains of S . pyogenes to bind fibrinogen enables them to escape the host defence mechanisms (Whitnack et al, 1984) and the strain of S . pyogenes used in the current study did bind fibrinogen very effectively (22% of the added protein).…”

“…Accordingly SMG strains were tested for their ability to adhere to saliva-coated hydroxy-apatite and buccal epithelial cells (Handley etal., 1987), to bind fibrinogen (Whitnack et al, 1984) and fibronectin (Abraham etal., 1983;Babu and Dabbous, 1986;Hogg and Manning, 1989), and to co-aggregate with strains of Veillonella and Actinomyces (Cisar et al, 1979;Weerkamp and McBride, 198 1). Hydrophobicity and surface charge may contribute to adhesion; therefore these properties were also investigated.…”