Tracing the evolutionary history of the pandemic group A streptococcal M1T1 clone

FASEB J. 2012 Nov;26(11):4675-84. doi: 10.1096/fj.12-212142. Epub 2012 Aug 9.


The past 50 years has witnessed the emergence of new viral and bacterial pathogens with global effect on human health. The hyperinvasive group A Streptococcus (GAS) M1T1 clone, first detected in the mid-1980s in the United States, has since disseminated worldwide and remains a major cause of severe invasive human infections. Although much is understood regarding the capacity of this pathogen to cause disease, much less is known of the precise evolutionary events selecting for its emergence. We used high-throughput technologies to sequence a World Health Organization strain collection of serotype M1 GAS and reconstructed its phylogeny based on the analysis of core genome single-nucleotide polymorphisms. We demonstrate that acquisition of a 36-kb genome segment from serotype M12 GAS and the bacteriophage-encoded DNase Sda1 led to increased virulence of the M1T1 precursor and occurred relatively early in the molecular evolutionary history of this strain. The more recent acquisition of the phage-encoded superantigen SpeA is likely to have provided selection advantage for the global dissemination of the M1T1 clone. This study provides an exemplar for the evolution and emergence of virulent clones from microbial populations existing commensally or causing only superficial infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biological Evolution*
  • Cell Line
  • Disease Models, Animal
  • Epithelial Cells / microbiology
  • Exotoxins / genetics
  • Exotoxins / metabolism
  • Gene Expression Regulation, Bacterial / physiology
  • Genome, Bacterial
  • Global Health
  • Host-Pathogen Interactions
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Neutrophils / physiology
  • Oligonucleotide Array Sequence Analysis
  • Pandemics*
  • Phagocytosis
  • Phylogeny
  • Streptococcal Infections / epidemiology*
  • Streptococcal Infections / microbiology*
  • Streptococcus pyogenes / classification
  • Streptococcus pyogenes / genetics
  • Streptococcus pyogenes / metabolism*
  • Streptococcus pyogenes / pathogenicity
  • Transcriptome
  • Virulence


  • Bacterial Proteins
  • Exotoxins
  • Membrane Proteins
  • SpeA protein, Streptococcus pyogenes