Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 group A Streptococcus. Academic Article uri icon

Overview

abstract

  • Whole-genome sequencing of serotype M3 group A streptococci (GAS) from oropharyngeal and invasive infections in Ontario recently showed that the gene encoding regulator of protease B (RopB) is highly polymorphic in this population. To test the hypothesis that ropB is under diversifying selective pressure among all serotype M3 GAS strains, we sequenced this gene in 1178 strains collected from different infection types, geographic regions, and time periods. The results confirmed our hypothesis and discovered a significant association between mutant ropB alleles, decreased activity of its major regulatory target SpeB, and pharyngitis. Additionally, isoallelic strains with ropB polymorphisms were significantly less virulent in a mouse model of necrotizing fasciitis. These studies provide a model strategy for applying whole-genome sequencing followed by deep single-gene sequencing to generate new insight to the rapid evolution and virulence regulation of human pathogens.

authors

  • Olsen, Randall
  • Laucirica, Daniel R
  • Watkins, M Ebru
  • Feske, Marsha L
  • Garcia-Bustillos, Jesus R
  • Vu, Chau
  • Cantu, Concepcion
  • Shelburne, Samuel A
  • Fittipaldi, Nahuel
  • Kumaraswami, Muthiah
  • Shea, Patrick R
  • Flores, Anthony R
  • Beres, Stephen B
  • Lovgren, Maguerite
  • Tyrrell, Gregory J
  • Efstratiou, Androulla
  • Low, Donald E
  • Van Beneden, Chris A
  • Musser, James Mallory

publication date

  • January 18, 2012

Research

keywords

  • Bacterial Proteins
  • Pharyngitis
  • Polymorphism, Genetic
  • Streptococcal Infections
  • Streptococcus pyogenes
  • Virulence Factors

Identity

PubMed Central ID

  • PMC4447876

Scopus Document Identifier

  • 84861033764

Digital Object Identifier (DOI)

  • 10.1093/infdis/jir825

PubMed ID

  • 22262791

Additional Document Info

volume

  • 205

issue

  • 11