SpyCEP in Clinical Streptococcus pyogenes Infection

Neutrophil chemoattractant interleukin (IL)–8 is cleaved and inactivated by the Streptococcus pyogenes cell envelope protease SpyCEP. A range of clinical S. pyogenes strains of differing emm type demonstrated SpyCEP activity, although transcription of the SpyCEP gene cepA differed 1000-fold between isolates. Disruption of the 2-component regulatory system covR/S in pharyngeal isolates increased cepA transcription 100-fold; this finding is consistent with endogenous CovR/S-mediated repression of cepA being responsible for low SpyCEP expression in some S. pyogenes strains associated with pharyngitis. Among patients with invasive S. pyogenes infection, disease severity and outcome were associated with the SpyCEP activity of the isolate. Lethal invasive isolate H292 (emm81) expressed more cepA than did other tested isolates. This strain carried a unique covR mutation that impaired binding to the cepA promoter. CovR/S sequence comparison in other clinical isolates revealed community-wide dissemination of covS mutations but not covR mutations. The results highlight a potential hazard and underline the importance of continuing molecular epidemiological surveillance for com-munity-wide dissemination of CovR/S mutant hyperinvasive strains. Streptococcus pyogenes (group A streptococcus [GAS]) causes a spectrum of infections, which range from phar-yngitis and impetigo to more-invasive life-threatening diseases, such as necrotizing fasciitis and toxic-shock syndrome [1]. Lethal S. pyogenes soft-tissue infections are associated with a paucity of neutrophils at the site of infection [2–4]. The S. pyogenes cell envelope pro-teinase SpyCEP can cleave and inactivate human in