Enzymatic properties, pathogenic potential, and prevalence of ExfA, a novel Staphylococcus felis exfoliative toxin

Exfoliative toxins (ETs) produced by staphylococci primarily target and cleave desmoglein 1 (Dsg1), a desmosomal adhesion molecule expressed in stratified squamous epithelia. A new ET gene was recently discovered in Staphylococcus felis, a commensal and opportunistic pathogen responsible for skin infections in Felidae. This study focused on characterizing ExfA, a protein encoded by this novel S. felis ET gene, examining its enzymatic characteristics, pathogenic potential, and prevalence. Recombinant ExfA eliminated immunofluorescence for Dsg1, but not for Dsg3, in the feline epidermis and directly digested the baculovirus-expressed extracellular segment of feline Dsg1. Additionally, recombinant ExfA digested mouse Dsg1α and Dsg1β, and when injected into neonatal mice, caused superficial epidermal splitting. Molecular modeling and docking analyses indicated that ExfA forms a closed oxyanion hole and is predicted to interact with the substrate in a manner similar to that of serine proteases. An epidemiological survey of feline skin isolates in Japan found that 46.7% of S. felis clinical isolates contained exfa, and culture supernatants from 71.4% of exfa-positive isolates digested feline Dsg1. In summary, S. felis ExfA demonstrates enzymatic activity that can degrade feline Dsg1, is frequently found in cat-derived S. felis strains, and may play a role in colonization and invasion of feline skin.