Genetic Switch to Hypervirulence Reduces Colonization Phenotypes of the Globally Disseminated Group A Streptococcus M1T1 Clone
A Hollands, MA Pence, AM Timmer… - The Journal of …, 2010 - academic.oup.com
The Journal of infectious diseases, 2010•academic.oup.com
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 …
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 …
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.
Oxford University Press