Small-Colony Variants of Staphylococcus aureus Persist in the Presence of Sub-lethal Doses of Hydrogen Peroxide

Abstract

Small-colony variants (SCVs) of Staphylococcus aureus are notorious for tolerating therapeutic doses of antimicrobials and persisting within host cells. However, the determinants of SCV formation are poorly understood. Understanding how S. aureus SCVs develop and endure is crucial as S. aureus infections are responsible for more deaths in the United States each year than AIDS. The study discussed here demonstrated S. aureus strains exposed to sub-lethal concentrations of hydrogen peroxide, a major component of immunity, exhibited a concentration-specific response and increase in the frequency of SCVs exhibiting gentamycin resistance. Pathways associated with the SOS response, including utilization of DNA double-strand break repair proteins RexAB, recombinase A, and polymerase V, mediated the survival of bacteria in the forms of SCVs. Exposure to hydrogen peroxide selected for the SCV phenotype, increased stability of the phenotype, and reduced the rate of reversion from SCV to wild-type colonies. SCVs also displayed increased catalase production compared to wild-type bacteria. As a whole, these findings clarify a potential mechanism for development and persistence of SCVs in human tissues.