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A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
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MsmR, a specific positive regulator of the Streptococcus pyogenes FCT pathogenicity region and cytolysin-mediated

Masanobu Nakata1, Andreas Podbielski, Bernd Kreikemeyer

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

Molecular Microbiology
|July 28, 2005
PubMed

Insights

Streptococcus pyogenes uses MsmR to regulate key adhesion and virulence factors, impacting bacterial attachment and host cell damage. This regulator, MsmR, balances bacterial spread and local infection by controlling gene expression in the FCT region.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Streptococcus pyogenes (group A streptococci, GAS) requires adherence to host cells for infection.
  • Adhesin genes, crucial for GAS colonization, are located in the FCT region of the genome.
  • Understanding GAS virulence factor regulation is key to controlling infections.

Purpose of the Study:

  • To identify and characterize transcriptional regulators within the FCT region of GAS.
  • To investigate the role of MsmR in regulating fibronectin-binding adhesins and virulence factors.
  • To elucidate the regulatory network controlling GAS adherence and cytotoxicity.

Main Methods:

  • Identification of MsmR as an AraC/XylS type transcriptional regulator in the FCT region.
  • Construction and analysis of an msmR mutant strain.
  • Transcriptome analysis and reporter fusion assays.
  • Electrophoretic mobility shift assays (EMSA) to confirm MsmR binding to promoter regions.

Main Results:

  • MsmR positively regulates the fibronectin-binding adhesin F2 and other FCT region genes, including Nra.
  • The msmR mutant exhibited reduced fibronectin binding, adherence, and internalization into human pharyngeal epithelial cells.
  • The mutant showed attenuated streptolysin O activity and cytotoxicity.
  • MsmR directly binds to the promoter regions of nga, nra/cpa, and prtF2.

Conclusions:

  • MsmR is a positive regulator of key GAS virulence factors, including adhesins and cytotoxins.
  • MsmR and Nra act antagonistically to fine-tune virulence gene expression in GAS.
  • This regulatory balance influences the interplay between local infection and bacterial dissemination.

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