M protein and protein F act as important determinants of cell-specific tropism of Streptococcus pyogenes in skin tissue.

Abstract

The pathogenic gram-positive bacterium Streptococcus pyogenes (group A streptococcus) causes numerous diseases of cutaneous tissue, each of which is initiated after the interaction of the bacterium with the cells of the epidermis. In this study, we show that different surface proteins of S. pyogenes play important roles in determining the cell-specific tropism of the bacterium in skin. Using streptococcal strains with defined mutations in the genes which encode surface proteins in combination with primary cultures of human skin and an in situ adherence assay which uses histological sections of human skin, we show that the M protein of S. pyogenes mediates the binding of the bacterium to keratinocytes, while a second streptococcal surface protein, protein F. directs the adherence of the organism to Langerhans' cells. Characterization of binding revealed that adherence was inhibited by purified streptococcal proteins and pretreatment of both host cells with the protease typsin. Adherence was only slightly affected by the state of keratinocyte differentiation in vitro, but was considerably modulated in response to environmental conditions known to regulate expression of M protein and protein F, suggesting that the interaction between these bacterial cell-surface structures/ adhesins and keratinocytes and Langerhans' cells may play an important role in streptococcal skin disease. (J. Clin. Invest. 1994. 94:965-977.)

Streptococcus pyogenes prtFII, but not sfbI, sfbII or fbp54, is represented more frequently among invasive-disease isolates of tropical Australia

“…pyogenes may utilize different adhesins for attachment and colonization of different tissues and for invasion. For instance, M protein may mediate adherence to keratinocytes in the epidermis, whereas SfbI may be necessary for adherence of group A streptococcus to pharyngeal cells and Langerhans' cells, a component of the basal layer of the epidermis [25]. Different repertoires of adhesins and their regulators, and the interactions of the adhesins with each other may determine tissue tropism and pathogenicity of S. pyogenes.…”

Bacterial determinants of persistent throat colonization and the associated immune response in a primate model of human group A streptococcal pharyngeal infection

“…Increased susceptibility to phagocytic killing in vitro may predict rapid phagocytic clearance of the M protein-deficient GAS strain from the throat in vivo. However, it is also possible that M protein-deficient GAS are rapidly cleared from the pharynx because they are defective in attachment to pharyngeal epithelia (Hasty et al, 1992;Okada et al, 1994;Schrager et al, 1998). The requirement for M protein in primate pharyngeal colonization was not predicted by previous studies in mice which demonstrated that M protein-deficient GAS were comparable with wildtype GAS in their ability to colonize the throat, but is consistent with the role of M protein as a critical virulence factor for the organism in in vitro phagocytic assays, murine intraperitoneal infection and murine invasive infection (Lancefield, 1962;Husmann et al, 1997;Moses et al, 1997;Ashbaugh et al, 1998).…”

A nonpetide integrin antagonist can inhibit epithelial cell ingestion of Streptococcus pyogenes by blocking formation of integrin α5β1-fibronectin-M1 protein complexes

“…For a number of strains, host cell entry requires bacterial binding of serum Fn. In these cases, bacterial-bound Fn appears to function as a bridging molecule, promoting bacterial interaction with host Fn receptors (13,16,17,19).…”