Streptococcal pyrogenic exotoxin B cleaves human S-adenosylhomocysteine hydrolase and induces hypermethioninemia.
Group A Streptococcus is a common pathogen that causes pharyngitis, impetigo, myositis, and lethal streptococcal toxic shock syndrome. Streptococcal pyrogenic exotoxin B (SPE B) is strongly associated with the severity of disease. SPE B is a cysteine protease and matures itself by autocatalysis. We found that SPE B was directly associated with human S-adenosylhomocysteine hydrolase (AdoHcyase), an essential factor for a delayed-type immune response. AdoHcyase protein levels and enzymatic activities were significantly higher in human cells infected with the Streptococcus pyogenes SW510 speB mutant strain than in cells infected with the NZ131 wild-type strain. SPE B also inactivated AdoHcyase, shown by a decrease in homocysteine, the main product of AdoHcyase. We found that in vivo and in vitro, SPE B induced hypermethioninemia, which is caused by an AdoHcyase defect. We also found that AdoHcyase is a substrate of SPE B cysteine protease. SPE B, therefore, potentially causes immunosuppression by cleaving AdoHcyase.
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
Ju-Fei
JF
Hsu
Woei-Jer
WJ
Chuang
Shu-Chu
SC
Shiesh
Yee-Shin
YS
Lin
Ching-Chuan
CC
Liu
Chih-Chieh
CC
Wang
Tzu-Fun
TF
Fu
Jui-He
JH
Tsai
Wei-Lun
WL
Tsai
Yu-Jun
YJ
Huang
Yi-Hsuan
YH
Hsieh
Jiunn-Jong
JJ
Wu
Ming T
MT
Lin
Wenya
W
Huang
D043383:Adenosylhomocysteinase / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D005098:Exotoxins / Q000378:metabolism*; D006801:Humans; D008715:Methionine / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D013290:Streptococcal Infections / Q000382:microbiology* / Q000473:pathology*; D013297:Streptococcus pyogenes / Q000201:enzymology*
D001426:Bacterial Proteins; D005098:Exotoxins; C027951:erythrogenic toxin; D008715:Methionine; D043383:Adenosylhomocysteinase