A 28-kilodalton fibronectin-binding protein of group a streptococci

Abstract

Lipoteichoic acid (LTA) has been implicated as a major adhesin of group A streptococci that interacts with fibronectin (Fn). It has been suggested that protein adhesins may also be involved in the binding of Fn to streptococci. We searched for such a protein by transblotting membrane preparations from M types 5, 19, and 24 group A streptococci to nitrocellulose and reacting the blot with 125I-Fn. The Fn reacted with a 28-kDa polypeptide from all three serotypes of streptococci. Using affinity-purified antibodies to the 28-kDa protein in immunoblots of membrane preparations from various streptococci, we demonstrated that the 28-kDa protein is present in all 17 strains tested. Affinity-purified antibodies to the 28-kDa protein also reacted in varying degrees with intact streptococci, demonstrating that the antigen is exposed on the surface of intact organisms. Our results suggest that, in addition to LTA, group A streptococci contain a common Fn-binding moiety that is expressed as a major component of membrane preparations and that is accessible on the surface of streptococci for interactions with Fn.

Pathogenesis of Group A Streptococcal Infections

“…Evidence suggested that LTA accounted for approximately 60% of adhesion to epithelial cells, indicating that other adhesins were involved in the adherence of group A streptococci to epithelial cells. In a recent review (226), Hasty and Courtney state that at least 11 adhesins have been described for group A streptococci, including M protein (90,136,168,169,401,540), LTA (106,109,111,398,488,489), protein F/Sfb (223, 224), a 29-kDa fibronectinbinding protein (105), glyceraldehyde-3-phosphate dehydrogenase (412,563), a 70-kDa galactose-binding protein (201,535), a vitronectin-binding protein (526), a collagen-binding protein (533), serum opacity factor (310), a 54-kDa fibronectin binding-protein, FBP54 (109), and the hyaluronate capsule (549). Several extracellular host cell proteins have been implicated in attachment or adherence to group A streptococci, including fibronectin (105,488), fibrinogen (463), collagen (533), vitronectin (526), a fucosylated glycoprotein (541), and integral membrane proteins including CD46, the membrane cofactor protein on keratinocytes (400), and CD44, the hyaluronatebinding receptor on keratinocytes (471).…”

Identification of a novel glycoprotein-binding activity in Streptococcus pyogenes regulated by the mga gene

“…Some of these, like the fibronectin-binding proteins (Talay et al, 1991(Talay et al, , 1992Courtney et al, 1992Courtney et al, , 1994Kreikemeyer et al, 1995 ;Rakonjac et al, 1995 ;Jaffe et al, 1996 ;Rocha & Fischetti, 1999), are adhesins, while others, for example M-like proteins (Cleary & Retnoningrum, 1994) and C5a peptidase (Chen & Cleary, 1990), are protective against the host immunodefence system. M-protein has a dual role, being the major antiphagocytic factor of S. pyogenes and also an adhesin that binds fibronectin, fibrinogen and albumin, among others (Fischetti et al, 1988 ;Schmidt et al, 1993 ;Gubbe et al, 1997).…”

Streptococcal M6 protein binds to fucose-containing glycoproteins on cultured human epithelial cells

“…A low antibody response to the N terminus of M protein (21) will enable the streptococcus to adhere to and to maintain contact with epithelial cells while other domains of the protein are complexed with complement factor H, fibrinogen, or immunoglobulins. The adhesion mediated by M protein may be augmented by the alternative adhesins lipoteichoic acid (35) and protein F (6,17,43), as suggested by the observation that Mstreptococci retain 25% of the adhesion activity for HEp-2 cells compared with an isogenic M+ strain (47). Similarly, adhesin of S. pyogenes DSM2071 to HEp-2 cells was inhibited by only 50% by a fusion protein containing the binding site of the streptococcal fibronectin-binding protein (43).…”