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Emerging role of the interleukin-8 cleaving enzyme SpyCEP in clinical Streptococcus pyogenes infection

Claire E Turner1, Prathiba Kurupati, Michael D Jones

  • 1Department of Infectious Diseases and Immunity, Imperial College London, Hammersmith Hospital, London, United Kingdom.

The Journal of Infectious Diseases
|July 14, 2009
PubMed

Insights

Streptococcus pyogenes protease SpyCEP inactivates interleukin-8. CovR/S mutations in Streptococcus pyogenes strains can increase SpyCEP activity, potentially leading to more severe invasive infections and community-wide spread.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Epidemiology

Background:

  • Neutrophil chemoattractant interleukin (IL)-8 is crucial for immune response.
  • Streptococcus pyogenes (group A Strep) possesses the cell envelope protease SpyCEP, which inactivates IL-8.
  • SpyCEP activity varies among clinical S. pyogenes isolates, impacting pathogenesis.

Purpose of the Study:

  • To investigate the regulation of SpyCEP gene (cepA) expression in S. pyogenes.
  • To determine the association between SpyCEP activity and invasive disease severity.
  • To assess the prevalence and dissemination of genetic factors influencing SpyCEP expression.

Main Methods:

  • Analysis of cepA transcription across diverse S. pyogenes strains.
  • Investigation of the role of the CovR/S two-component regulatory system in cepA regulation.
  • Sequence comparison of covR/S genes in clinical isolates.
  • Correlation of SpyCEP activity with clinical outcomes in invasive infections.

Main Results:

  • cepA transcription varied significantly (1000-fold) among isolates.
  • Disruption of CovR/S system increased cepA transcription (100-fold), indicating CovR/S-mediated repression.
  • CovR/S mutations, particularly in covS, were widespread in clinical isolates.
  • High SpyCEP activity correlated with lethal invasive infections, exemplified by strain H292 with a covR mutation.

Conclusions:

  • CovR/S regulatory system plays a key role in controlling SpyCEP expression in S. pyogenes.
  • Mutations in CovR/S can lead to increased SpyCEP activity and potentially hypervirulent strains.
  • Community-wide dissemination of CovR/S mutant strains poses a public health risk.
  • Molecular epidemiological surveillance is essential to monitor these hyperinvasive strains.

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