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M1T1 group A streptococcal pili promote epithelial colonization but diminish systemic virulence through neutrophil

Laura E Crotty Alexander1, Heather C Maisey, Anjuli M Timmer

  • 1Department of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

Journal of Molecular Medicine (Berlin, Germany)
|December 5, 2009
PubMed

Insights

Group A Streptococcus pili enhance adherence but reduce systemic virulence. Pili induce neutrophil responses, leading to bacterial entrapment and killing within extracellular traps.

Area of Science:

  • Microbiology
  • Pathogenesis
  • Immunology

Background:

  • Group A Streptococcus (GAS) is a significant human pathogen causing various infections.
  • Pili, cell wall-anchored appendages, have been identified in pathogenic streptococci and shown to aid adherence.

Purpose of the Study:

  • To investigate the role of pilus expression in the virulence of the M1T1 GAS clone.
  • To determine how pili affect GAS adherence, systemic infection, and host immune responses.

Main Methods:

  • Targeted mutagenesis to create GAS strains with altered pilus expression.
  • In vitro assays for adherence to epithelial and skin cells.
  • Murine models for necrotizing fasciitis, pneumonia, and sepsis.
  • In vitro assays for survival in human blood and neutrophil interactions.

Main Results:

  • Pilus expression enhanced GAS adherence to pharyngeal cells, keratinocytes, and skin.
  • Contrary to expectations, pilus expression reduced GAS virulence in murine systemic infection models and decreased survival in human blood.
  • GAS pili induced neutrophil IL-8 production, promoted neutrophil transcytosis, and increased extracellular trap formation, leading to bacterial entrapment and killing.

Conclusions:

  • GAS pili play a dual role: promoting adherence but attenuating systemic virulence.
  • Pilus-mediated induction of neutrophil extracellular traps is a key mechanism for GAS clearance during invasive infections.
  • Targeting pili may offer a novel strategy to combat severe GAS infections.

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