Interplay of Staphylococcal and Host Proteases Promotes Skin Barrier Disruption in Netherton Syndrome.
Adolescent
Adult
Animals
Bacterial Toxins
/ metabolism
Child
Colony Count, Microbial
Epidermis
Female
Humans
Male
Mice, Inbred C57BL
Microbiota
Middle Aged
Netherton Syndrome
/ enzymology
Peptide Hydrolases
/ metabolism
Phenols
Skin
/ microbiology
Solubility
Staphylococcus aureus
/ enzymology
Staphylococcus epidermidis
/ enzymology
Netherton syndrome
S. aureus
S. epidermidis
epidermal barrier
proteases
skin inflammation
skin microbiome
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
03 03 2020
03 03 2020
Historique:
received:
29
10
2019
revised:
04
12
2019
accepted:
05
02
2020
entrez:
5
3
2020
pubmed:
5
3
2020
medline:
25
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32130897
pii: S2211-1247(20)30175-3
doi: 10.1016/j.celrep.2020.02.021
pmc: PMC7183042
mid: NIHMS1571421
pii:
doi:
Substances chimiques
Bacterial Toxins
0
Phenols
0
staphylococcal delta toxin
0
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2923-2933.e7Subventions
Organisme : NIAID NIH HHS
ID : R37 AI052453
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR074302
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR076082
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI152038
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR069653
Pays : United States
Organisme : BLRD VA
ID : I01 BX002711
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI117673
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests R.L.G. is a co-founder, scientific advisor, consultant, and has equity in MatriSys Biosciences and is a consultant, receives income, and has equity in Sente. All other authors declare no competing interests.
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