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Evolution in fast forward: a potential role for mutators in accelerating Staphylococcus aureus pathoadaptation
Gregory S Canfield1, Johanna M Schwingel, Matthew H Foley
1Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Journal of Bacteriology
|December 4, 2012
Summary
Mutator strains of Staphylococcus aureus, with defects in DNA repair systems, accelerate the evolution of virulence. These "mutators" enhance pathogen survival and persistence during chronic infections without increased sensitivity to reactive oxygen species.
Area of Science:
- Microbiology
- Genetics
- Evolutionary Biology
Background:
- Pathogen evolution and phenotypic changes are crucial for survival during chronic infections.
- Staphylococcus aureus utilizes DNA repair systems to maintain genome stability.
Purpose of the Study:
- To investigate the role of DNA repair system mutations (mutators) in Staphylococcus aureus pathoadaptation.
- To determine if defects in mismatch repair (MMR) and oxidized guanine (GO) systems impact mutation rates and virulence.
Main Methods:
- Genetic and phenotypic characterization of S. aureus strains with induced MMR and GO mutations.
- Analysis of spontaneous mutation frequencies, types, and hot spots.
- Assessment of hydrogen peroxide sensitivity.
- Measurement of virulence factor (α-hemolysin, staphyloxanthin) inactivation rates during serial passage.
Main Results:
- Mutator strains exhibited increased and altered spontaneous mutation frequencies, consistent with MMR or GO loss.
- No increased sensitivity to hydrogen peroxide was observed in these DNA repair mutants.
- GO and MMR mutants showed accelerated inactivation rates of α-hemolysin and staphyloxanthin, indicating modified virulence phenotypes.
Conclusions:
- Defects in DNA repair systems (mutators) in S. aureus can accelerate the evolution of virulence phenotypes.
- Mutators may drive pathogen adaptation and contribute to persistent infections by rapidly altering traits like α-hemolysin and staphyloxanthin production.
- The absence of increased oxidative stress sensitivity suggests mutators can evolve within the host environment.
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