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Inhibition of cysteine protease and growth of Staphylococcus aureus V8 and poliovirus by phosphorylated cystatin α conjugate of skin

The inhibitory properties of phosphorylated cystatin α (P‐cystatin α) and a conjugated protein of the P‐cystatin α with filaggrin linker segment peptide (FLSP) against the growth of Staphylococcus bacteria and poliovirus were investigated. Both the P‐cystatin α and the conjugated protein (P‐cystatin α‐FLSP conjugate) as a model for the cornified envelope of skin inhibited the cysteine protease activity of Staphylococcus aureus V8. The protease activity was inhibited by normal cornified envelope of newborn rat skin, which contains P‐cystatin α, and P‐cystatin α in cornified envelope of newborn rat skin also suppressed the growth of S. aureus V8. When P‐cystatin α or P‐cystatin α‐FLSP conjugate was added to cultured HeLa cells infected with poliovirus, 50—70% of the cell‐death due to poliovirus infection was prevented. The poliovirus 3C protease activity in the infected HeLa cells was inhibited by P‐cystatin α or P‐cystatin α‐FLSP conjugate. As a result, the processing of viral capsid peptides was suppressed. These findings suggest that P‐cystatin α and P‐cystatin α‐FLSP conjugate could play the role of the barrier against microorganism infections due to inhibition of their cysteine protease activities.