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Updated: Jun 2, 2026

Invasion of Human Cells by a Bacterial Pathogen
07:15

Invasion of Human Cells by a Bacterial Pathogen

Published on: March 21, 2011

Streptococcus pyogenes M49 plasminogen/plasmin binding facilitates keratinocyte invasion via integrin-integrin-linked

Nikolai Siemens1, Nadja Patenge, Juliane Otto

  • 1Institute of Medical Microbiology, Virology and Hygiene, Rostock University Hospital, Schillingallee 70, 18057 Rostock, Germany.

The Journal of Biological Chemistry
|April 28, 2011
PubMed

Insights

Streptococcus pyogenes (group A streptococci, GAS) invades skin cells via plasminogen-mediated, integrin-dependent uptake. This interaction also protects GAS bacteria from immune cell destruction.

Area of Science:

  • Microbiology
  • Cell Biology
  • Immunology

Background:

  • Streptococcus pyogenes (group A streptococci, GAS) requires epithelial cell entry for host colonization and infection.
  • Understanding GAS invasion mechanisms is crucial for developing effective countermeasures.

Purpose of the Study:

  • To elucidate the mechanism of GAS internalization into keratinocytes.
  • To identify key host cell receptors and signaling pathways involved in GAS invasion.
  • To investigate the role of plasminogen in GAS survival against host defenses.

Main Methods:

  • Investigated GAS interaction with human keratinocytes.
  • Utilized integrin-blocking antibodies and siRNA to identify host receptors (α(1)β(1) and α(5)β(1)-integrins).
  • Employed kinase inhibitors (ILK, PI3K, Akt) and actin polymerization blockers to study signaling pathways.
  • Assessed bacterial survival after opsonization and macrophage phagocytosis.

Main Results:

  • GAS interaction with plasminogen promotes integrin-mediated internalization into keratinocytes, independent of plasmin protease activity.
  • α(1)β(1) and α(5)β(1)-integrins are identified as primary keratinocyte receptors for GAS.
  • Inhibition of ILK, PI3K, Akt, and actin polymerization significantly reduced GAS invasion.
  • Plasminogen binding confers protection to GAS against macrophage-mediated killing.

Conclusions:

  • A novel model for plasminogen-mediated GAS invasion into keratinocytes is proposed, highlighting integrin signaling.
  • Plasminogen binding serves a dual role: facilitating bacterial entry and evading innate immunity.

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