Degradation of bradykinin by a metalloendopeptidase from Streptococcus pyogenes

Yoichi Miyamoto, Takaaki Akaike, Shigetada Kawabata, Teruo Akuta, Chiho Taruki, Jun Yoshitake, Shigeyuki Hamada, Fusao Ota, Hideo Igarashi, Kentaro Yoshimura, Ryutaro Kamijo, Hiroshi Maeda

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)167-172
Number of pages6
Journaljournal of oral biosciences
Volume58
Issue number4
DOIs
Publication statusPublished - 2016 Nov 1

Keywords

  • Bradykinin
  • Peptidase
  • Streptococcus pyogenes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dentistry(all)

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