Measurement of protease activity of exfoliative toxin A using synthetic peptidyl substrates and correlation between in vivo and in vitro activities
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Exfoliative toxin A (ETA) produced by Staphylococcus aureus causes bullous impetigo and staphylococcal scalded skin syndrome. The exfoliative activity of ETA is ascribed to its highly restricted degradation between Glu381-Gly382 of desmoglein 1, a component protein of desmosomes. Since the peptidase activity of ETA has been yet to be demonstrated other than desmoglein 1, the entity as a peptidase and its molecular mechanism remain to be elucidated. In the present study, we determined the peptidase activity using recombinant ETA molecules and synthetic fluorescent peptidyl substrates, while the exfoliative activity was examined by a neonatal mouse model. Although peptidase activity was trivial as compared with the S. aureus glutamyl endopeptidase GluV8, pro-ETA starting from Phe24 (Phe24-ETA) and the mature form from Glu39 (Glu39-ETA) exhibited the activities toward LLE-, AE-, and LE-MCA, but not toward LLQ-, LD- or AAA-MCA, indicating a Glu-specific endopeptidase activity. This activity was statistically higher in Glu39-ETA than Phe24-ETA and was inhibited by the serine protease inhibitor Pefabloc. Deletion of the α1 region at positions 42-56 as well as substitution of active Ser233 to Ala abrogated the peptidase activity. In accord with these results, intraepidermal blister formation and epidermolysis were induced more exclusively by Glu39-ETA than Phe24-ETA. ETAs without proteolytic activity as well as GluV8 did not cause an exfoliative reaction. These results suggest that the highly restricted Glu-specific endopeptidase activity of ETA is involved in exfoliative activity and that the α1 region is required for these functions.
- Nagasaki University School of Medicineの論文
- 2013-08-00
Nagasaki University School of Medicine | 論文
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