title: Genetic switch to hypervirulence reduces colonization phenotypes of the globally disseminated group A streptococcus M1T1 clone.
abstract: BACKGROUND
  The recent resurgence of invasive group A streptococcal disease has been paralleled by the emergence of the M1T1 clone. Recently, invasive disease initiation has been linked to mutations in the covR/S 2-component regulator. We investigated whether a fitness cost is associated with the covS mutation that counterbalances hypervirulence.
  
  
  METHODS
  Wild-type M1T1 group A Streptococcus and an isogenic covS-mutant strain derived from animal passage were compared for adherence to human laryngeal epithelial cells, human keratinocytes, or fibronectin; biofilm formation; and binding to intact mouse skin. Targeted mutagenesis of capsule expression of both strains was performed for analysis of its unique contribution to the observed phenotypes.
  
  
  RESULTS
  The covS-mutant bacteria showed reduced capacity to bind to epithelial cell layers as a consequence of increased capsule expression. The covS-mutant strain also had reduced capacity to bind fibronectin and to form biofilms on plastic and epithelial cell layers. A defect in skin adherence of the covS-mutant strain was demonstrated in a murine model.
  
  
  CONCLUSIONS
  Reduced colonization capacity provides a potential explanation for why the covS mutation, which confers hypervirulence, has not become fixed in the globally disseminated M1T1 group A Streptococcus clone, but rather may arise anew under innate immune selection in individual patients.
authors.affiliation: School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hollands
authors.forename: Morgan A
authors.initials: MA
authors.lastname: Pence
authors.forename: Anjuli M
authors.initials: AM
authors.lastname: Timmer
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Osvath
authors.forename: Lynne
authors.initials: L
authors.lastname: Turnbull
authors.forename: Cynthia B
authors.initials: CB
authors.lastname: Whitchurch
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Walker
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000382:microbiology; D051379:Mice; D010641:Phenotype; D011485:Protein Binding; D012867:Skin / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D005353:Fibronectins