Contribution ofhlaRegulation by SaeR toStaphylococcus aureusUSA300 Pathogenesis
ABSTRACTThe SaeRS two-component system inStaphylococcus aureusis critical for regulation of many virulence genes, includinghla, which encodes alpha-toxin. However, the impact of regulation of alpha-toxin by Sae onS. aureuspathogenesis has not been directly addressed. Here, we mutated the SaeR-binding sequences in thehlaregulatory region and determined the contribution of this mutation tohlaexpression and pathogenesis in strain USA300 JE2. Western blot analyses revealed drastic reduction of alpha-toxin levels in the culture supernatants of SaeR-binding mutant in contrast to the marked alpha-toxin production in the wild type. The SaeR-binding mutation had no significant effect on alpha-toxin regulation by Agr, MgrA, and CcpA. In animal studies, we found that the SaeR-binding mutation did not contribute to USA300 JE2 pathogenesis using a rat infective endocarditis model. However, in a rat skin and soft tissue infection model, the abscesses on rats infected with the mutant were significantly smaller than the abscesses on those infected with the wild type but similar to the abscesses on those infected with asaeRmutant. These studies indicated that there is a direct effect ofhlaregulation by SaeR on pathogenesis but that the effect depends on the animal model used.