IdeS, a novel streptococcal cysteine proteinase with unique specificity for immunoglobulin G.
Recent work from several laboratories has demonstrated that proteolytic mechanisms significantly contribute to the molecular interplay between Streptococcus pyogenes, an important human pathogen, and its host. Here we describe the identification, purification and characterization of a novel extracellular cysteine proteinase produced by S.pyogenes. This enzyme, designated IdeS for Immunoglobulin G-degrading enzyme of S.pyogenes, is distinct from the well-characterized streptococcal cysteine proteinase, SpeB, and cleaves human IgG in the hinge region with a high degree of specificity. Thus, other human proteins, including immunoglobulins M, A, D and E, are not degraded by IdeS. The enzyme efficiently cleaves IgG antibodies bound to streptococcal surface structures, thereby inhibiting the killing of S.pyogenes by phagocytic cells. This and additional observations on the distribution and expression of the ideS gene indicate that IdeS represents a novel and significant bacterial virulence determinant, and a potential therapeutic target.
von Pawel-Rammingen
Ulrich
U
Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, BMC, B14, SE-221 84 Lund, Sweden. Ulrich.von_Pawel@medkem.lu.se
Johansson
Björn P
BP
Björck
Lars
L
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000145:classification / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D015870:Gene Expression; D005798:Genes, Bacterial; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D016023:Integrins / Q000145:classification / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology; D010587:Phagocytosis / Q000276:immunology; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000276:immunology; D013379:Substrate Specificity
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016023:Integrins; C442815:Mac-1-like protein, Streptococcus; D003546:Cysteine Endopeptidases; C042477:streptopain