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Updated: May 26, 2026

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
07:10

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues

Published on: February 19, 2019

A protease-sensing circuit links neutrophil inflammation to virulence regulation in Streptococcus pyogenes

Stephanie Guerra1,2, Ananya Dash1,3, Doris L LaRock1

  • 1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA.

Biorxiv : the Preprint Server for Biology
|May 25, 2026
PubMed

Insights

Neutrophil extracellular traps (NETs) promote Streptococcus pyogenes virulence factor SpeB expression by degrading repressors. This interaction drives severe disease, highlighting a mutual host-pathogen counterattack.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Streptococcus pyogenes causes severe diseases like scarlet fever and toxic shock syndrome.
  • The virulence factor SpeB protease contributes to hyperinflammation during S. pyogenes infections.
  • The feedback loop between inflammation and SpeB expression remains largely unknown.

Purpose of the Study:

  • To investigate the interplay between neutrophil extracellular traps (NETs) and SpeB expression in S. pyogenes.
  • To elucidate the regulatory mechanisms controlling SpeB induction during infection.

Main Methods:

  • Investigated the interaction between NETosis and speB gene induction.
  • Analyzed the role of neutrophil proteases and bacterial protein Vfr in speB regulation.
  • Utilized in vivo models with abrogated NET formation or neutrophil depletion.

Main Results:

  • Neutrophil proteases released during NETosis degrade the repressor Vfr, relieving speB repression.
  • The cathelicidin peptide LL-37 normally represses speB via the CovRS system, but this is overcome by NETosis.
  • SpeB also autoregulates its expression by degrading Vfr at high bacterial densities.
  • In vivo, blocking NETs or depleting neutrophils led to speB repression.

Conclusions:

  • NETosis is a key inducer of S. pyogenes speB expression.
  • A mutual counterattack between host NETs and bacterial virulence factors drives severe disease pathology.
  • Targeting this interaction could offer therapeutic strategies for S. pyogenes infections.
Keywords:
Streptococcus pyogenesgene regulationinnate immunityinvasive infectionneutrophil extracellular trapsneutrophilsproteasevirulence factor

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