A molecular trigger for intercontinental epidemics of group A Streptococcus. Academic Article uri icon

Overview

abstract

  • The identification of the molecular events responsible for strain emergence, enhanced virulence, and epidemicity has been a long-pursued goal in infectious diseases research. A recent analysis of 3,615 genomes of serotype M1 group A Streptococcus strains (the so-called "flesh-eating" bacterium) identified a recombination event that coincides with the global M1 pandemic beginning in the early 1980s. Here, we have shown that the allelic variation that results from this recombination event, which replaces the chromosomal region encoding secreted NADase and streptolysin O, is the key driver of increased toxin production and enhanced infection severity of the M1 pandemic strains. Using isoallelic mutant strains, we found that 3 polymorphisms in this toxin gene region increase resistance to killing by human polymorphonuclear leukocytes, increase bacterial proliferation, and increase virulence in animal models of pharyngitis and necrotizing fasciitis. Genome sequencing of an additional 1,125 streptococcal strains and virulence studies revealed that a highly similar recombinational replacement event underlies an ongoing intercontinental epidemic of serotype M89 group A Streptococcus infections. By identifying the molecular changes that enhance upper respiratory tract fitness, increased resistance to innate immunity, and increased tissue destruction, we describe a mechanism that underpins epidemic streptococcal infections, which have affected many millions of people.

publication date

  • August 10, 2015

Research

keywords

  • NAD+ Nucleosidase
  • Pandemics
  • Polymorphism, Genetic
  • Streptococcal Infections
  • Streptococcus pyogenes
  • Virulence Factors

Identity

PubMed Central ID

  • PMC4588293

Scopus Document Identifier

  • 84941625090

Digital Object Identifier (DOI)

  • 10.1159/000360478

PubMed ID

  • 26258415

Additional Document Info

volume

  • 125

issue

  • 9