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Proapoptotic effect of proteolytic activation of matrix metalloproteinases by Streptococcus pyogenes thiol proteinase

Fumio Tamura1, Rumiko Nakagawa, Teruo Akuta

  • 1Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.

Infection and Immunity
|July 24, 2004
PubMed

Insights

Streptococcus pyogenes thiol proteinase (SpeB) activates matrix metalloproteinases (MMPs), leading to host cell apoptosis via tumor necrosis factor alpha and soluble Fas ligand release. This mechanism contributes to S. pyogenes infection severity.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Streptococcus pyogenes thiol proteinase (SpeB) is a key virulence factor.
  • SpeB induces host cell apoptosis, but its mechanism remains unclear.

Purpose of the Study:

  • Investigate the role of matrix metalloproteinases (MMPs) in SpeB-induced apoptosis.
  • Elucidate the molecular mechanisms underlying SpeB's pro-apoptotic effects.

Main Methods:

  • Produced recombinant SpeB and human pro-MMP-9/-2.
  • Assessed MMP activation and cytokine release (TNF-alpha, sFasL) using enzyme immunoassays and cell cultures.
  • Utilized an in vivo murine model of S. pyogenes infection.

Main Results:

  • SpeB activated proMMP-9 and proMMP-2.
  • SpeB-activated MMPs induced TNF-alpha and sFasL release, promoting apoptosis in U937 cells.
  • SpeB directly caused TNF-alpha and sFasL release and MMP production in vivo.

Conclusions:

  • SpeB-activated MMPs contribute to S. pyogenes pathogenesis.
  • Extracellular release of TNF-alpha and sFasL by SpeB and activated MMPs drives tissue damage and invasion.

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