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Identifying genetic determinants of Streptococcus pyogenes-host interactions in a murine intact skin infection model

Reid V Wilkening1, Christophe Langouët-Astrié2, Morgan M Severn3

  • 1Section of Pediatric Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Microbiology and Immunology, University of Colorado School of Medicine, Aurora, CO 80045, USA.

Cell Reports
|October 27, 2023
PubMed

Insights

Streptococcus pyogenes adapts genetically to infect mouse skin, activating a quorum-sensing system. This system is crucial for persistent infection, increasing disease severity and inflammation.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Genomics

Background:

  • Streptococcus pyogenes is a significant human pathogen responsible for various infections.
  • Understanding host-pathogen interactions is crucial for developing effective treatments.

Purpose of the Study:

  • To develop a murine model for studying Streptococcus pyogenes epithelial infection.
  • To investigate the genetic adaptations of S. pyogenes and host responses during infection.
  • To determine the role of the Rgg2/Rgg3 quorum-sensing system in S. pyogenes skin infections.

Main Methods:

  • Development of a murine model with intact epithelium for S. pyogenes infection.
  • RNA sequencing to analyze host and bacterial gene expression at 5 and 24 hours post-infection.
  • Experimental manipulation of the Rgg2/Rgg3 quorum-sensing system.

Main Results:

  • S. pyogenes undergoes genetic adaptation, including metabolic changes and Rgg2/Rgg3 quorum-sensing activation, to infect murine epithelium.
  • An intact Rgg2/Rgg3 quorum-sensing cascade is essential for establishing a stable superficial skin infection.
  • Activation of the quorum-sensing system leads to increased murine morbidity, bacterial burden, skin changes, and inflammation.

Conclusions:

  • The developed murine model effectively simulates S. pyogenes epithelial interactions.
  • The Rgg2/Rgg3 quorum-sensing pathway is critical for persistent S. pyogenes skin infections.
  • Targeting the quorum-sensing system may offer a therapeutic strategy against S. pyogenes infections.
Keywords:
CP: MicrobiologyNZ131RNA-seqRgg2/Rgg3Streptococcus pyogenesanimal modelshost responsequorum sensingskin infectiontranscriptome

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