STREPTOCOCCAL CYSTEINE PROTEINASE RELEASES KININS - A NOVEL VIRULENCEMECHANISM

Previous work has indicated a crucial role for the extracellular cyste ine proteinase of Streptococcus pyogenes in the pathogenicity and viru lence of this important human pathogen. Here we find that the purified streptococcal cysteine proteinase releases biologically active kinins from their purified precursor protein, H-kininogen, in vitro, and fro m kininogens man plasma, ex vivo. Kinin liberation in tf lr plasma is due to the direct action of the streptococcal proteinase on the kinino gens, and does not involve the previous activation of plasma prekallik rein, the physiological plasma kininogenase. Judged from the amount of released plasma kinins the bacterial proteinase is highly efficient i ll its action. This is also the case in vivo. Injection of the purifie d cysteine proteinase into the peritoneal cavity oi mice resulted in a progressive cleavage of plasma kininogens and the concomitant release of kinins over a period of 5 h. No kininogen degradation was seen ill mice when the cysteine proteinase was inactivated by the specific inh ibitor, Z-Leu-Val-Gly-CHN2, before administration. Intraperitoneal adm inistration into mice of living S. pyogenes bacteria producing the cys teine proteinase induced a rapid breakdown of endogenous plasma kinino gens and release of kinins. Kinins are hypotensive, they increase vasc ular permeability, contract smooth muscle, and induce fever and pain. The release of kinins by the cysteine proteinase of S. Pyogenes could therefore represent an important and previously unknown virulence mech anism in S. pyogenes infections.