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 skinsyndrome. The exfoliative activity of ETA is ascribed to its highly restricted degradation between Glu381-Gly382 of desmoglein1, a component protein of desmosomes. Since the peptidase activity of ETA has been yet to be demonstrated other than desmoglein1, the entity as a peptidase and its molecular mechanism remain to be elucidated. In the present study, we determinedthe peptidase activity using recombinant ETA molecules and synthetic fluorescent peptidyl substrates, while the exfoliativeactivity was examined by a neonatal mouse model. Although peptidase activity was trivial as compared with the S. aureusglutamyl 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 endopeptidaseactivity. This activity was statistically higher in Glu39-ETA than Phe24-ETA and was inhibited by the serine proteaseinhibitor Pefabloc. Deletion of the α1 region at positions 42-56 as well as substitution of active Ser233 to Ala abrogatedthe peptidase activity. In accord with these results, intraepidermal blister formation and epidermolysis were induced moreexclusively by Glu39-ETA than Phe24-ETA. ETAs without proteolytic activity as well as GluV8 did not cause an exfoliativereaction. These results suggest that the highly restricted Glu-specific endopeptidase activity of ETA is involved in exfoliativeactivity and that the α1 region is required for these functions.
長崎大学医学部の論文

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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長崎大学医学部 | 論文

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