title: Emerging role of the interleukin-8 cleaving enzyme SpyCEP in clinical Streptococcus pyogenes infection.
abstract: 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 community-wide dissemination of CovR/S mutant hyperinvasive strains.
authors: Department of Infectious Diseases and Immunity, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Claire E
authors: CE
authors: Turner
authors: Prathiba
authors: P
authors: Kurupati
authors: Michael D
authors: MD
authors: Jones
authors: Robert J
authors: RJ
authors: Edwards
authors: Shiranee
authors: S
authors: Sriskandan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D000071677:Histidine Kinase; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013290:Streptococcal Infections / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000145:classification / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C534547:CovS protein, Streptococcus pyogenes; D000071677:Histidine Kinase; D010447:Peptide Hydrolases; C527349:SpyCEP protein, Streptococcus pyogenes