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Updated: Jun 12, 2026
Generation of a Gene-disrupted Streptococcus mutans Strain Without Gene Cloning
Published on: October 23, 2017
Genetic switch to hypervirulence reduces colonization phenotypes of the globally disseminated group A streptococcus
Andrew Hollands1, Morgan A Pence, Anjuli M Timmer
1School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
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.
Conclusion:
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.
Insights
The covS mutation in M1T1 group A Streptococcus increases virulence but reduces bacterial colonization. This fitness cost explains why the hypervirulent covS mutant may not become fixed in the population.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- The M1T1 clone of group A Streptococcus is associated with a resurgence of invasive disease.
- Mutations in the covR/S 2-component regulator have been linked to invasive disease initiation.
- The study investigates a potential fitness cost associated with covS mutations that may counterbalance hypervirulence.
Purpose of the Study:
- To determine if the covS mutation in M1T1 group A Streptococcus incurs a fitness cost.
- To compare the adherence, biofilm formation, and skin binding capabilities of wild-type and covS-mutant strains.
- To analyze the contribution of capsule expression to observed phenotypes.
Main Methods:
- Comparison of wild-type M1T1 group A Streptococcus and an isogenic covS-mutant strain.
- Assessment of adherence to human epithelial cells and keratinocytes, and fibronectin binding.
- Evaluation of biofilm formation and binding to intact mouse skin.
- Targeted mutagenesis of capsule expression for phenotype analysis.
Main Results:
- The covS-mutant strain exhibited reduced adherence to epithelial cells due to increased capsule expression.
- Impaired binding to fibronectin and reduced biofilm formation were observed in the covS-mutant.
- The covS-mutant strain demonstrated defective skin adherence in a murine model.
Conclusions:
- Reduced colonization capacity is a potential explanation for the limited fixation of the hypervirulent covS mutation in the M1T1 clone.
- The covS mutation may arise transiently under innate immune selection in individual patients.
- This suggests a dynamic interplay between virulence and colonization in pathogen evolution.
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