Skin-Derived SPINK9 Kills Escherichia coli

Area of Science:

• Dermatology
• Microbiology
• Biochemistry

Background:

• Antimicrobial peptides are crucial for skin's defense against microbes.
• The stratum corneum, the outermost skin layer, harbors antimicrobial factors.
• Understanding these factors is key to skin's innate immunity.

Purpose of the Study:

• To identify and characterize novel antibacterial factors in the human stratum corneum.
• To investigate the specific antibacterial activity and mechanism of identified factors.
• To explore the role of these factors in skin's protective barrier function.

Main Methods:

• Isolation and identification of proteins from healthy stratum corneum.
• Biochemical assays to determine enzyme inhibition and antibacterial activity.
• Bacterial genetics and electron microscopy to elucidate the killing mechanism.
• Identification of bacterial interaction partners.

Main Results:

• SPINK9, a kallikrein-related peptidase inhibitor, was identified as a major antibacterial factor.
• Specific N-terminal variants of SPINK9 selectively killed Escherichia coli strains.
• SPINK9 entered bacterial cells and its activity was modulated by the bacterial chaperone SKP.
• Killing activity correlated with the peptidase inhibition sequence.

Conclusions:

• SPINK9 is an epidermal antimicrobial peptide with selective bactericidal activity against E. coli.
• SPINK9 contributes to the innate barrier function of human skin.
• The interaction with bacterial chaperones like SKP influences SPINK9's efficacy.