Protein exfoliative D (ETD) of Staphylococcus aureus: inactivation / activation by synthetic peptides and characterization of complexes

Abstract

Virulent strains of Staphylococcus aureus secrete virulence factors that may play important roles in bacterial establishment and proliferation. Among them, exfoliative toxins (ETs), found in 4 isoforms (ETA, ETB, ETC and ETD), are exotoxins that cause loss of cell adhesion in the epidermis of several organisms, causing Staphylococcal Scalded Skin Syndrome (SSSS). S. aureus ETs are serine proteinases that exhibit high specificity for their substrates and their extremely complex mechanisms of action allow bacteria to penetrate the epidermis, facilitating the efficient progression of infection. Desmoglein 1, a protein responsible for cell adhesion in the epidermis, is selectively cleaved by ETs. Residues located between positions 271 and 277 of human and murine Dsg1 are crucial for cleavage of the peptide bond of this substrate between Glu381 and Gly382 residues. Five of these residues are involved in the coupling of the ETs to the Dsgs and will be used as the basis for the design of synthetic peptides that interact specifically with the ETD.