Interplay of Staphylococcal and Host Proteases Promotes Skin Barrier Disruption in Netherton Syndrome.

Cell Reports
Michael R WilliamsRichard L Gallo

Abstract

Netherton syndrome (NS) is a monogenic skin disease resulting from loss of function of lymphoepithelial Kazal-type-related protease inhibitor (LEKTI-1). In this study we examine if bacteria residing on the skin are influenced by the loss of LEKTI-1 and if interaction between this human gene and resident bacteria contributes to skin disease. Shotgun sequencing of the skin microbiome demonstrates that lesional skin of NS subjects is dominated by Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). Isolates of either species from NS subjects are able to induce skin inflammation and barrier damage on mice. These microbes promote skin inflammation in the setting of LEKTI-1 deficiency due to excess proteolytic activity promoted by S. aureus phenol-soluble modulin α as well as increased bacterial proteases staphopain A and B from S. aureus or EcpA from S. epidermidis. These findings demonstrate the critical need for maintaining homeostasis of host and microbial proteases to prevent a human skin disease.

Citations

Nov 13, 2020·PLoS Pathogens·Morgan M Brown, Alexander R Horswill
Jun 20, 2020·The Journal of Investigative Dermatology·Verena Moosbrugger-MartinzSandrine Dubrac
Jul 8, 2020·The Journal of Allergy and Clinical Immunology·Laura CauRichard L Gallo
Apr 3, 2021·Frontiers in Immunology·Astrid HendriksElisabetta Soldaini
Jul 13, 2021·Experimental Dermatology·Mahendran Chinnappan, Tamia A Harris-Tryon
Aug 14, 2020·Cell Host & Microbe·Laurice Flowers, Elizabeth A Grice

Dec 4, 2020·Annales de dermatologie et de vénéréologie·A Pham-Ledard
Sep 21, 2021·The Journal of Allergy and Clinical Immunology·Claire BarbieuxAlain Hovnanian

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Datasets Mentioned

BETA
PRJNA551026
CAD61962.1
AAG45844.1
AJ298299

Methods Mentioned

BETA
genetic modifications
phylogenetic profiling
genetic modification
Transfection
PCR
FRET

Software Mentioned

ggplot2
GraphPad Prism
QUAST
Blast
HMMER
CLC Assembly Cell (
R
PhyloDB
reshape2
dplyr

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