Degradation of bradykinin by a metalloendopeptidase from Streptococcus pyogenes.

Objectives: Streptococcus pyogenes secretes streptococcal pyrogenic exotoxin B (SpeB), which cleaves kininogen to liberate bradykinin. In addition, this bacterium also has cell-associated bradykinin-degrading activity. Here, we characterized the bradykinin-degrading enzyme produced by S. pyogenes.

Methods: The effects of various peptidase inhibitors on bradykinin degradation by intact S. pyogenes and cell lysates were assessed. Cleavage of bradykinin and other peptides by a recombinant putative metalloendopeptidase (Sp-Pep) from S. pyogenes was analyzed by mass spectrometry. The enhancement of vascular permeability induced by bradykinin (before and after treatment with Sp-Pep) was evaluated in guinea pig skin.

Results: Various S. pyogenes strains expressed Sp-Pep. Immunoadsorption of S. pyogenes with an anti-Sp-Pep antibody showed that 80% of the bradykinin-degrading activity in S. pyogenes was due to Sp-Pep. Recombinant Sp-Pep cleaved bradykinin, and cleavage caused a loss of its extravasation-inducing potential. Sp-Pep-mediated degradation of bradykinin was 40 times more efficient than degradation of substance P and angiotensin II. While S. pyogenes secreted mature SpeB in stationary phase, this bacterium produced Sp-Pep during all tested growth phases.

Conclusions: S. pyogenes produces a cell-associated metalloendopeptidase that degrades bradykinin.