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.
Hsu
Ju-Fei
JF
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
Chuang
Woei-Jer
WJ
Shiesh
Shu-Chu
SC
Lin
Yee-Shin
YS
Liu
Ching-Chuan
CC
Wang
Chih-Chieh
CC
Fu
Tzu-Fun
TF
Tsai
Jui-He
JH
Tsai
Wei-Lun
WL
Huang
Yu-Jun
YJ
Hsieh
Yi-Hsuan
YH
Wu
Jiunn-Jong
JJ
Lin
Ming T
MT
Huang
Wenya
W
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