Defining the Strain-Dependent Impact of the Staphylococcal Accessory Regulator ( sarA ) on the Alpha-Toxin Phenotype of Staphylococcus aureus

We demonstrate that mutation of the staphylococcal accessory regulator (sarA ) limits the accumulation of alpha-toxin and phenol-soluble modulins (PSMs) inStaphylococcus aureus isolates of the USA300 clonal lineage. Degradation assays and experiments done with protease inhibitors suggested that this was due to the increased production of extracellular proteases rather than differences associated with the impact ofsarA on transcription of the target gene (hla ) or the accessory gene regulator (agr ). This was confirmed by demonstrating that concomitant mutation of the gene encoding aureolysin (aur ) reversed the alpha-toxin and PSM-deficient phenotypes of a USA300sarA mutant. Mutation ofsarA had little impact on the alpha-toxin or PSM phenotypes of the commonly studied strain Newman, which is known to have a mutation insaeS that results in constitutive activation of thesaeRS regulatory system, and we also demonstrate that repair of this defect resulted in the increased production of extracellular proteases and reversed both the alpha-toxin and PSM-positive phenotypes of a NewmansarA mutant.