title: The deficient cleavage of M protein-bound IgG by IdeS: insight into the escape of Streptococcus pyogenes from antibody-mediated immunity.
abstract: IdeS (IgG-degrading enzyme of Streptococcus pyogenes) is a virulence factor for S. pyogenes, group A Streptococcus (GAS). IdeS is believed to allow GAS to evade antibody-mediated phagocytosis by cleaving IgG at the lower hinge region. Human immunoglobulins bind to the GAS surface by two mechanisms: Specific antibodies attach at the Fab region to their specific antigens on the bacterial surface. Immunoglobulins can also attach nonspecifically at the Fc region to streptococcal M and M-like proteins. This phenomenon is believed to form the host-like coat and to block the recognition of Fc region by Fc receptor on phagocytes and antibody-dependent cell-mediated cytotoxicity. It is not known whether IdeS preferentially cleaves IgG attached at the Fab or Fc regions. To explore this issue, we used Sepharose beads coated with protein A or L or M protein as surrogate markers for specific (Fab) and nonspecific (Fc) binding sites. We found that IdeS cleaved Fab-bound IgG as rapidly as soluble IgG. In contrast, Fc-bound IgG was cleaved about 4 fold less than soluble IgG. In a competitive binding assay, we found that M protein had a greater affinity than IdeS to attach to the Fc region of human IgG. Thus, IdeS exhibited preferential IgG endopeptidase activity for Fab-bound IgG while allowing the non-specific binding of IgG to remain attached to M protein. We propose that this preferential enzymatic activity accounts for the ability of GAS to resist immunoglobulin-mediated phagocytosis and cytotoxicity.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Su
authors.forename: Woei-Jer
authors.initials: WJ
authors.lastname: Chuang
authors.forename: Shih-Min
authors.initials: SM
authors.lastname: Wang
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Chen
authors.forename: Chuan
authors.initials: C
authors.lastname: Chiang-Ni
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
authors.forename: Jiunn-Jong
authors.initials: JJ
authors.lastname: Wu
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Liu
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D015139:Blotting, Southern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013297:Streptococcus pyogenes / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D007074:Immunoglobulin G; C442815:Mac-1-like protein, Streptococcus; C014689:streptococcal M protein