Mutational analysis confirms the presence of a positively controlled virulence regulon in the OF+ lineage of S. pyogenes. Although there are differences in the organization of the virR regulon in OF+ and OF- strains, expression of these surface proteins is dependent on a VirR protein. In addition, it appears that production of OF is dependent on virR. The contribution of OF to the pathogenesis of S. pyogenes is unknown. The greater association of OF+ strains with impetigo compared to the greater association of OF- strains with pharyngitis  may indicate that production of apoproteinase is a contributing factor to skin infections.