Streptococcal pyrogenic exotoxin B cleaves properdin and inhibits complement-mediated opsonophagocytosis.
Streptococcal pyrogenic exotoxin B (SPE B), a cysteine protease, is an important virulence factor in group A streptococcal (GAS) infection. The reduction of phagocytic activity by SPE B may help prevent bacteria from being ingested. In this study, we investigated the mechanism SPE B uses to enable bacteria to resist opsonophagocytosis. Using Western blotting and an affinity column immobilized with SPE B, we found that both SPE B and C192S, an SPE B mutant lacking protease activity, bound to serum properdin, and that SPE B, but not C192S, degraded serum properdin. Further study showed that SPE B-treated, but not C192S-treated, serum blocked the alternative complement pathway. Reconstitution of properdin into SPE B-treated serum unblocked the alternative pathway. GAS opsonized with SPE B-treated serum was more resistant to neutrophil killing than GAS opsonized with C192S-treated or normal serum. These results suggest that a novel SPE B mechanism, one which degrades serum properdin, enables GAS to resist opsonophagocytosis.
Tsao
Nina
N
Department of Biological Science and Technology, I-Shou University, Kaohsiung County, Taiwan.
Tsai
Wan-Hua
WH
Lin
Yee-Shin
YS
Chuang
Woei-Jer
WJ
Wang
Chiou-Huey
CH
Kuo
Chih-Feng
CF
D000818:Animals; D001665:Binding Sites; D003165:Complement System Proteins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism* / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009895:Opsonin Proteins / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects*; D011414:Properdin / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D013290:Streptococcal Infections / Q000378:metabolism* / Q000517:prevention & control
D009895:Opsonin Proteins; D011414:Properdin; D003165:Complement System Proteins; D003546:Cysteine Endopeptidases; C042477:streptopain