title: Degradation of complement 3 by streptococcal pyrogenic exotoxin B inhibits complement activation and neutrophil opsonophagocytosis.
abstract: Streptococcal pyrogenic exotoxin B (SPE B), a cysteine protease, is an important virulence factor in group A streptococcus (GAS) infection. The inhibition of phagocytic activity by SPE B may help prevent bacteria from being ingested. In this study, we examined the mechanism SPE B uses to enable bacteria to resist opsonophagocytosis. Using an enzyme-linked immunosorbent assay, we found that SPE B-treated serum impaired the activation of the classical, the lectin, and the alternative complement pathways. In contrast, C192S, a SPE B mutant lacking protease activity, had no effect on complement activation. Further study showed that cleavage of serum C3 by SPE B, but not C192S, blocked zymosan-induced production of reactive oxygen species in neutrophils as a result of decreased deposition of C3 fragments on the zymosan surface. Reconstitution of C3 into SPE B-treated serum unblocked zymosan-mediated neutrophil activation dose dependently. SPE B-treated, but not C192S-treated, serum also impaired opsonization of C3 fragments on the surface of GAS strain A20. Moreover, the amount of C3 fragments on the A20 cell surface, a SPE B-producing strain, was less than that on its isogenic mutant strain, SW507, after opsonization with normal serum. A20 opsonized with SPE B-treated serum was more resistant to neutrophil killing than A20 opsonized with normal serum, and SPE B-mediated resistance was C3 dependent. These results suggest a novel SPE B mechanism, one which degrades serum C3 and enables GAS to resist complement damage and opsonophagocytosis.
authors.affiliation: Department of Nursing, I-Shou University, Kaohsiung County, Taiwan.
authors.forename: Chih-Feng
authors.initials: CF
authors.lastname: Kuo
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
authors.forename: Woei-Jer
authors.initials: WJ
authors.lastname: Chuang
authors.forename: Jiunn-Jong
authors.initials: JJ
authors.lastname: Wu
authors.forename: Nina
authors.initials: N
authors.lastname: Tsao
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005098:Exotoxins / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000276:immunology* / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D003176:Complement C3; D005098:Exotoxins; D050505:Mutant Proteins; D017382:Reactive Oxygen Species; C027951:erythrogenic toxin