Degradation of Complement 3 by Streptococcal Pyrogenic Exotoxin B Inhibits Complement Activation and Neutrophil Opsonophagocytosis

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 bact...

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Bibliographic Details
Published in:Infection and Immunity 2008-03, Vol.76 (3), p.1163-1169
Main Authors: Kuo, Chih-Feng, Lin, Yee-Shin, Chuang, Woei-Jer, Wu, Jiunn-Jong, Tsao, Nina
Format: Article
Language:English
Subjects:
Amino Acid Substitution - genetics
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bacteriology
Biological and medical sciences
Complement Activation - immunology
Complement C3 - antagonists & inhibitors
Complement C3 - metabolism
Exotoxins - genetics
Exotoxins - metabolism
Fundamental and applied biological sciences. Psychology
Host Response and Inflammation
Microbiology
Mutant Proteins - genetics
Mutant Proteins - metabolism
Neutrophil Activation - immunology
Neutrophils - immunology
Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains
Phagocytosis - immunology
Reactive Oxygen Species - immunology
Reactive Oxygen Species - metabolism
Streptococcus
Streptococcus pyogenes - immunology
Streptococcus pyogenes - physiology
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Summary: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.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.01116-07