A matrix form of fibronectin mediates enhanced binding of Streptococcus pyogenes to host tissue.
The pathogenic Gram-positive bacterium Streptococcus pyogenes (group A streptococcus) binds to fibronectin via protein F. In this study, we have investigated the binding properties of protein F to various multimeric tissue forms of fibronectin that appear on cell surfaces and in the extracellular matrix. We show that binding of S. pyogenes through protein F is more efficient to an in vitro-derived polymerized form of fibronectin (superfibronectin) than to soluble fibronectin immobilized in a solid phase. In addition, Chinese hamster ovary cells overexpressing the alpha5beta1 integrin produced an increased amount of a fibronectin matrix and consequently bound a higher number of S. pyogenes cells. Inhibition and direct binding assays using purified proteins demonstrated that binding to a fibronectin matrix involved both domains of protein F (UR and RD2) that have previously been implicated in interactions with fibronectin. Using intact S. pyogenes bacteria in which various domains of protein F were expressed as hybrids with the surface-exposed region of an unrelated protein, we revealed that, in contrast to the predominantly UR-mediated binding to soluble fibronectin, the maximal binding to the fibronectin matrix required RD2 in addition to UR. Since in some infections S. pyogenes may initially encounter a matrix form of fibronectin, these results suggest that UR and RD2 may be important for the initiation of streptococcal infectious processes.
Okada
N
N
Department of Bacteriology, Institute of Medical Science, University of Tokyo, Tokyo 108, Japan. okada@ims.u-tokyo.ac.jp
Watarai
M
M
Ozeri
V
V
Hanski
E
E
Caparon
M
M
Sasakawa
C
C
D018829:Adhesins, Bacterial / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D001665:Binding Sites; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D005353:Fibronectins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D017469:Receptors, Fibronectin / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013045:Species Specificity; D013297:Streptococcus pyogenes / Q000502:physiology*; D014162:Transfection
D018829:Adhesins, Bacterial; D005353:Fibronectins; D017469:Receptors, Fibronectin; D011994:Recombinant Proteins; C078635:fibronectin-binding proteins, bacterial