TY - JOUR
T1 - Streptococcal pyrogenic exotoxin B cleaves human S-adenosylhomocysteine hydrolase and induces hypermethioninemia
AU - Hsu, Ju Fei
AU - Chuang, Woei Jer
AU - Shiesh, Shu Chu
AU - Lin, Yee Shin
AU - Liu, Ching Chuan
AU - Wang, Chih Chieh
AU - Fu, Tzu N.
AU - Tsai, Jui He
AU - Tsai, Wei Lun
AU - Huang, Yu Jun
AU - Hsieh, Yi Hsuan
AU - Wu, Jiunn Jong
AU - Lin, Ming T.
AU - Huang, Wenya
N1 - Funding Information:
Received 3 October 2007; accepted 14 February 2008; electronically published 2 June 2008. Potential conflicts of interest: none reported. Financial support: National Health Research Institute Taiwan (grant NHRI-EX95-9429SP to Y.S.L.). Reprints or correspondence: Wenya Huang, PhD, Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, No. 1 University Road, Tainan 70101, Taiwan ([email protected]).
PY - 2008/8/1
Y1 - 2008/8/1
N2 - 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.
AB - 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.
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U2 - 10.1086/589719
DO - 10.1086/589719
M3 - Article
C2 - 18522500
AN - SCOPUS:48749124234
SN - 0022-1899
VL - 198
SP - 367
EP - 374
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -