Fc-mediated nonspecific binding between fibronectin-binding protein I of Streptococcus pyogenes and human immunoglobulins.
Fibronectin-binding protein I (SfbI) from Streptococcus pyogenes plays a key role in bacterial adhesion to, and invasion of, eukaryotic cells. In addition, SfbI exhibits a considerable potential as mucosal adjuvant and can trigger polyclonal activation of B cells. Here, we report that SfbI is also capable of binding human IgG in a nonimmune fashion. SfbI was reactive with IgG1, IgG2, IgG3, and IgG4 isotypes (type IIo IgG-binding profile). The affinity constant (Kd) of the SfbI-IgG interaction was in the range of 1-2 x 10(-5) M. Further studies demonstrated that the SfbI binding was mediated by the Fc component of the IgG molecule. Experiments performed using purified recombinant proteins spanning different domains of SfbI showed that the IgG-binding activity was restricted to the fibronectin-binding domains, and in particular to the fibronectin-binding repeats. Finally, the presence of recombinant SfbI resulted in an impairment of both phagocytosis of IgG-coated RBCs and Ab-dependent cell cytotoxicity by macrophages. These results demonstrated for the first time that, in addition to its major role during the colonization process, SfbI may also favor bacterial immune evasion after the onset of the infection by interfering with host clearance mechanisms.
Medina
E
E
Department of Microbial Pathogenicity and Vaccine Research, Division of Microbiology, GBF-National Research Center for Biotechnology, Braunschweig, Germany.
Molinari
G
G
Rohde
M
M
Haase
B
B
Chhatwal
G S
GS
Guzmán
C A
CA
D018829:Adhesins, Bacterial; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D001666:Binding Sites, Antibody; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism / Q000502:physiology*; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000382:microbiology
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D005353:Fibronectins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007136:Immunoglobulins; D010446:Peptide Fragments; C078635:fibronectin-binding proteins, bacterial