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Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
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Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells

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A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues

Carlos Hidalgo-Grass1, Inbal Mishalian, Mary Dan-Goor

  • 1Institute of Microbiology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.

The EMBO Journal
|September 16, 2006
PubMed

Insights

Group A Streptococcus uses the ScpC enzyme to degrade immune signals, preventing polymorphonuclear leukocytes (PMNs) from reaching infection sites. This impairs the innate immune response, making ScpC a key factor in necrotizing fasciitis virulence.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Group A Streptococcus (GAS) causes severe necrotizing fasciitis (NF).
  • Reduced polymorphonuclear leukocyte (PMN) infiltration observed in NF infections.
  • GAS serine peptidase implicated in degrading the chemokine IL-8, hindering PMN recruitment.

Purpose of the Study:

  • Identify the specific GAS serine peptidase responsible for immune evasion.
  • Investigate the regulation of this peptidase.
  • Determine the role of this peptidase in GAS virulence and NF pathogenesis.

Main Methods:

  • Bioinformatics analysis to predict the peptidase.
  • Targeted mutagenesis to create deficient GAS strains.
  • In vitro degradation assays of chemokines.
  • Murine model of necrotizing fasciitis to assess virulence.

Main Results:

  • The GAS serine peptidase was identified as ScpC.
  • ScpC transcription is downregulated by the SilCR pheromone via the SilA/B two-component system.
  • ScpC degrades human IL-8, murine KC, and MIP-2 chemokines in vitro.
  • ScpC is essential for GAS virulence in a murine NF model; ScpC-deficient mutants are non-virulent in immunocompetent mice but lethal in PMN-depleted mice.
  • ScpC inhibits PMN recruitment by degrading chemokines in infected tissues.

Conclusions:

  • ScpC is a novel and essential GAS virulence factor.
  • ScpC directly inactivates key components of the host innate immune response, specifically CXC chemokines.
  • ScpC facilitates GAS survival and pathogenesis by blocking PMN infiltration into infected tissues.

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