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Specific C-terminal cleavage and inactivation of interleukin-8 by invasive disease isolates of Streptococcus pyogenes

Robert J Edwards1, Graham W Taylor, Melissa Ferguson

  • 1Section of Experimental Medicine and Toxicology, Faculty of Medicine, Imperial College London, London, United Kingdom.

The Journal of Infectious Diseases
|August 10, 2005
PubMed

Insights

Streptococcus pyogenes degrades interleukin-8 (IL-8), a key neutrophil attractant, hindering the immune response in necrotizing fasciitis. This bacterial immune evasion mechanism prevents neutrophil recruitment to infection sites.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Necrotizing fasciitis caused by Streptococcus pyogenes exhibits a notable lack of neutrophils at infection sites.
  • Interleukin-8 (IL-8) is crucial for neutrophil migration and activation but can be degraded by S. pyogenes.

Purpose of the Study:

  • To investigate the mechanism by which S. pyogenes degrades IL-8.
  • To identify the bacterial factor responsible for IL-8 degradation.
  • To understand how this degradation impacts neutrophil recruitment during infection.

Main Methods:

  • Comparison of IL-8 degradation by blood and throat isolates of S. pyogenes.
  • Analysis of the specific cleavage site within the IL-8 molecule.
  • Biochemical fractionation of bacterial supernatant to isolate the enzyme responsible for IL-8 cleavage.
  • Association of IL-8-cleaving activity with S. pyogenes cell envelope proteinase (SpyCEP).

Main Results:

  • Blood isolates of S. pyogenes demonstrated superior IL-8 degradation compared to throat isolates.
  • IL-8 degradation occurred via a specific cleavage between glutamine-59 and arginine-60 in the IL-8 C-terminal alpha helix.
  • Degraded IL-8 showed reduced capacity to activate and migrate neutrophils.
  • IL-8-cleaving activity was localized to a 150-kDa fraction containing SpyCEP.

Conclusions:

  • S. pyogenes possesses an unprecedented immune evasion strategy involving the cleavage and inactivation of IL-8.
  • The bacterial enzyme SpyCEP is responsible for this IL-8 degradation.
  • This mechanism effectively prevents neutrophil recruitment, contributing to the pathogenesis of severe S. pyogenes infections like necrotizing fasciitis.

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