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J Invest Dermatol. 2019 May;139(5):1135-1142. doi: 10.1016/j.jid.2018.11.004. Epub 2018 Nov 20.

Skin-Derived SPINK9 Kills Escherichia coli.

Author information

1
School of Biological and Chemical Engineering/Zhejiang Provincial Key Lab for Chem & Bio Processing Technology of Farm Products, Zhejiang University of Science and Technology, Hangzhou, China; Department of Dermatology, University-Hospital Schleswig-Holstein, Kiel, Germany.
2
School of Biological and Chemical Engineering/Zhejiang Provincial Key Lab for Chem & Bio Processing Technology of Farm Products, Zhejiang University of Science and Technology, Hangzhou, China.
3
Department of Dermatology, University-Hospital Schleswig-Holstein, Kiel, Germany.
4
Department of Dermatology, University-Hospital Schleswig-Holstein, Kiel, Germany. Electronic address: umeyerhoffert@dermatology.uni-kiel.de.

Abstract

Antimicrobial peptides play a critical role in the barrier function of human skin. They offer a fast response to invading microorganisms and protect from external microbial infection. Here we show the isolation of the kallikrein-related peptidase inhibitor SPINK9 as a major antibacterial factor from healthy stratum corneum. In total, six N-terminal SPINK9 variants were identified in the stratum corneum. Whereas all variants exhibited similar inhibition activities against kallikrein-related peptidase, only three variants with either lysine or glutamine as their first N-terminal residues were able to kill various Escherichia coli strains, but not other bacteria or fungi. The killing activity also depended on the sequence essential for kallikrein-related peptidase inhibition. Ultrastructural electron microscopy analyses suggested that SPINK9 entered the cell and killed growing bacteria. A bacterial chaperone, SKP, was identified as the major SPINK9 interacting partner in E. coli cells. The Skp-deleted mutant was more sensitive to SPINK9 than the wild-type control, suggesting that the bactericidal activity of SPINK9 should first overcome the resistance from the bacterial chaperone SKP. Thus, SPINK9 is a member of epidermal antimicrobial peptides for selective killing of E. coli, which might contribute to the innate barrier function of human skin.

PMID:
30468739
DOI:
10.1016/j.jid.2018.11.004

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