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

doi:10.1016/j.job.2016.07.003

Degradation of bradykinin by a metalloendopeptidase from Streptococcus pyogenes

J Oral Biosci. 2016 Nov;58(4):167-172. doi: 10.1016/j.job.2016.07.003. Epub 2016 Aug 2.

Authors

Affiliations

¹ Department of Microbiology, Kumamoto University School of Medicine, Kumamoto, Japan. Electronic address: yoichim@dent.showa-u.ac.jp.
² Department of Microbiology, Kumamoto University School of Medicine, Kumamoto, Japan.
³ Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan.
⁴ Department of Food Microbiology, The University of Tokushima School of Medicine, Tokushima, Japan.
⁵ Institute of Food Hygiene, Snow Brand Milk Products, Co., Ltd., Saitama, Japan.
⁶ Department of Biochemistry, Showa University School of Dentistry, Tokyo, Japan.

PMID: 32512685
DOI: 10.1016/j.job.2016.07.003

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.

Keywords: Bradykinin; Peptidase; Streptococcus pyogenes.