Cleavage of antigen-bound immunoglobulin G by SpeB contributes to streptococcal persistence in opsonizing blood.
Group A streptococci (GAS) express a superantigen, SpeB, having cysteine protease activity. SpeB exhibits several properties that might contribute to virulence, the most recently discovered being the ability to cleave immunoglobulin G (IgG) in a manner similar to that of papain. In the present study, we confirmed this latter finding and found that the irreversible inhibition of SpeB protease activity completely abolishes IgG cleavage. SpeB cleavage of IgG was not species restricted since SpeB cleaved both human, rabbit, and mouse IgG. In order to investigate the nature of the SpeB cleavage of IgG, antibodies were immobilized prior to exposure to SpeB, either by unspecific binding of the Fc to GAS surface proteins or by antigen-specific binding. Analysis of the IgG molecules by SDS-PAGE showed that SpeB could cleave antigen-bound antibodies, while the IgG bound to IgG-binding proteins was protected from cleavage. In a phagocytosis assay using whole blood, the M49 GAS strain NZ131 showed a significantly higher survival than its isogenic speB mutant. Furthermore, the addition of extracellular supernatant derived from an overnight culture of native NZ131 increased the survival of its isogenic speB derivative. This indicates that SpeB's ability to cleave off the Fc part of antigen-bound IgG contributes to GAS escape from opsonophagocytosis while not interfering with the formation of a host-like coat by unspecific IgG binding.
Eriksson
Anna
A
Department of Biomedical Laboratory of Science, Umeå University, S-901 85 Umeå, Sweden. anna.eriksoon@climi.umu.se
Norgren
Mari
M
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001769:Blood / Q000382:microbiology*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism*; D051379:Mice; D009895:Opsonin Proteins / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology*; D011817:Rabbits; D013297:Streptococcus pyogenes / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D003546:Cysteine Endopeptidases; C042477:streptopain