Genetic switch to hypervirulence reduces colonization phenotypes of the globally disseminated group A streptococcus M1T1 clone.
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.
Hollands
Andrew
A
School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
Pence
Morgan A
MA
Timmer
Anjuli M
AM
Osvath
Sarah R
SR
Turnbull
Lynne
L
Whitchurch
Cynthia B
CB
Walker
Mark J
MJ
Nizet
Victor
V
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
D005353:Fibronectins