Dissection of the molecular basis for hypervirulence of an in vivo-selected phenotype of the widely disseminated M1T1 strain of group A Streptococcus bacteria

J Infect Dis. 2010 Mar 15;201(6):855-65. doi: 10.1086/651019.


Group A streptococci (GAS) may engage different sets of virulence strategies, depending on the site of infection and host context. We previously isolated 2 phenotypic variants of a globally disseminated M1T1 GAS clone: a virulent wild-type (WT) strain, characterized by a SpeB(+)/SpeA(-)/Sda1(low) phenotype, and a hypervirulent animal-passaged (AP) strain, better adapted to survive in vivo, with a SpeB(-)/SpeA(+)/Sda1(high) phenotype. This AP strain arises in vivo due to the selection of bacteria with mutations in covS, the sensor part of a key 2-component regulatory system, CovR/S. To determine whether covS mutations explain the hypervirulence of the AP strain, we deleted covS from WT bacteria (DeltaCovS) and were able to simulate the hypervirulence and gene expression phenotype of naturally selected AP bacteria. Correction of the covS mutation in AP bacteria reverted them back to the WT phenotype. Our data confirm that covS plays a direct role in regulating GAS virulence.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Cysteine Endopeptidases / biosynthesis
  • Cysteine Endopeptidases / genetics
  • Deoxyribonuclease I / biosynthesis
  • Deoxyribonuclease I / genetics
  • Exotoxins / biosynthesis
  • Exotoxins / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial
  • Histidine Kinase
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Kaplan-Meier Estimate
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred CBA
  • Mutation
  • Phenotype
  • Polymerase Chain Reaction
  • Streptococcal Infections / microbiology
  • Streptococcus pyogenes / genetics*
  • Streptococcus pyogenes / pathogenicity*
  • Virulence


  • Bacterial Proteins
  • Exotoxins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • SpeA protein, Streptococcus pyogenes
  • CovS protein, Streptococcus pyogenes
  • Histidine Kinase
  • Deoxyribonuclease I
  • Sda1 protein, Streptococcus pyogenes
  • Cysteine Endopeptidases
  • streptopain