Staphylococcal exfoliative toxins cleave alpha- and beta-melanocyte-stimulating hormones

The staphylococcal exfoliative toxins (ETs) A and B (ETA and ETB) are 27-kD a exotoxins produced by certain strains of Staphylococcus aureus and are th e causative agents of staphylococcal scalded-skin syndrome. The crystal str uctures of the ETs strongly indicate that the proteins are members of the s erine protease family of enzymes, although protease activity until now has not yet been conclusively demonstrated. Here, we show that the peptide beta -melanocyte-stimulating hormone (beta-MSH) is cleaved by ETA and that both ETA and ETB are capable of cleaving alpha-MSH. Both toxins exhibit cleavage at specific glutamic acid residues in MSH peptides. Moreover, biologically inactive mutants of ETA were incapable of cleaving beta-MSH.