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Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 group A

Randall J Olsen1, Daniel R Laucirica, M Ebru Watkins

  • 1Department of Pathology and Laboratory Medicine, The Methodist Hospital Research Institute, Houston, TX, USA. rjolsen@tmhs.org

The Journal of Infectious Diseases
|January 21, 2012
PubMed

Insights

The regulator of protease B (RopB) gene in group A streptococci (GAS) shows significant diversity, linked to reduced virulence and pharyngitis. This finding offers insights into pathogen evolution and disease regulation.

Area of Science:

  • Microbiology
  • Genetics
  • Infectious Diseases

Background:

  • Serotype M3 group A streptococci (GAS) are significant human pathogens.
  • Previous whole-genome sequencing revealed high polymorphism in the regulator of protease B (RopB) gene in Ontario GAS strains.

Purpose of the Study:

  • To investigate the hypothesis that the ropB gene is under diversifying selective pressure across all serotype M3 GAS strains.
  • To determine the association between ropB polymorphisms, SpeB activity, and disease presentation (pharyngitis).
  • To evaluate the impact of ropB polymorphisms on GAS virulence in a preclinical model.

Main Methods:

  • Sequencing of the ropB gene in 1178 serotype M3 GAS strains from diverse sources.
  • Analysis of the association between ropB alleles, SpeB activity, and clinical data.
  • Virulence assessment of isoallelic strains in a mouse model of necrotizing fasciitis.

Main Results:

  • The ropB gene is indeed under diversifying selective pressure in serotype M3 GAS.
  • Mutant ropB alleles significantly correlate with decreased SpeB activity and pharyngitis.
  • GAS strains with ropB polymorphisms exhibited reduced virulence in a mouse model.

Conclusions:

  • The ropB gene's diversity is linked to altered virulence and disease tropism in GAS.
  • Whole-genome sequencing followed by single-gene sequencing is an effective strategy for studying pathogen evolution.
  • Findings provide insights into the rapid evolution and virulence regulation of human pathogens.

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