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Interplay of Staphylococcal and Host Proteases Promotes Skin Barrier Disruption in Netherton Syndrome
- Source :
- Cell Reports, Vol 30, Iss 9, Pp 2923-2933.e7 (2020), Cell reports, vol 30, iss 9, Cell reports
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- SUMMARY 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.<br />Graphical Abstract<br />In Brief Williams et al. show how an abnormal skin microbiome promotes inflammation associated with Netherton syndrome, a monogenic disorder in the human protease inhibitor SPINK5. Subjects with Netherton syndrome have excess colonization by S. aureus or S. epidermidis that then produce and promote increased protease production in the epidermis.
- Subjects :
- Male
0301 basic medicine
Medical Physiology
Colony Count, Microbial
Human skin
medicine.disease_cause
0302 clinical medicine
Staphylococcus epidermidis
Child
lcsh:QH301-705.5
Skin
biology
epidermal barrier
integumentary system
Microbiota
Middle Aged
Staphylococcus aureus
Female
Adult
Proteases
Adolescent
Bacterial Toxins
Article
General Biochemistry, Genetics and Molecular Biology
Microbiology
03 medical and health sciences
Phenols
skin inflammation
medicine
Animals
Humans
Staphopain
Netherton syndrome
Protease inhibitor (pharmacology)
Microbiome
medicine.disease
biology.organism_classification
S. aureus
S. epidermidis
Mice, Inbred C57BL
030104 developmental biology
Solubility
lcsh:Biology (General)
Netherton Syndrome
proteases
skin microbiome
Biochemistry and Cell Biology
Epidermis
030217 neurology & neurosurgery
Peptide Hydrolases
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 30
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....f84dd85ae5b65580f73c6a9c51bde3e4