Targeting of desmoglein 1 in exfoliative toxin-mediated disease

Cory L. Simpson; Kathleen J. Green; Spiro Getsios

doi:10.1586/edm.10.62

Targeting of desmoglein 1 in exfoliative toxin-mediated disease

Cory L. Simpson, Kathleen J. Green, Spiro Getsios

Research output: Contribution to journal › Review article › peer-review

Abstract

Exfoliative toxin (ET) is secreted by Staphylococcus aureus and has long been known to cause localized or widespread epidermal blistering in humans termed bullous impetigo or staphylococcal scalded-skin syndrome, respectively. While initial hypotheses suggested that ET was a superantigen, sequence and crystallographic analysis characterized the toxin as a serine protease. More recent work determined that ET cleaves a desmosomal cadherin, desmoglein (Dsg)1. This discovery explained the mechanism of toxin-induced blistering, since Dsg1 proteolysis compromises desmosomes, which link keratinocytes and support epidermal integrity. Here, we review clinical findings in ET-mediated disease, the characterization of ET, the molecular pathogenesis of bullous impetigo/staphylococcal scalded-skin syndrome, the structure and function of Dsg1, and current and potential treatments of ET-mediated disease.

Original language	English (US)
Pages (from-to)	659-670
Number of pages	12
Journal	Expert Review of Dermatology
Volume	5
Issue number	6
DOIs	https://doi.org/10.1586/edm.10.62
State	Published - Dec 2010

Funding

Diseases (NIH R01 AR041836) and by an endowment from the Joseph L Mayberry Foundation. Spiro Getsios is supported by a Career Development Award from the Dermatology Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Cory L Simpson is supported by a Kirschstein National Research Service Award from the National Institute of Environmental Health Sciences (NIH F30 ES14990), a Presidential Fellowship from Northwestern University and a Malkin Family Scholarship from the Robert H Lurie Comprehensive Cancer Center of Northwestern University. Kathleen J Green is supported by research grants from the National Institute of Arthritis and Musculoskeletal and Skin

Keywords

Staphylococcus aureus
bullous impetigo
desmoglein
desmosomal cadherin
desmosome
exfoliative toxin
staphylococcal scalded-skin syndrome

ASJC Scopus subject areas

Dermatology

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10.1586/edm.10.62

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title = "Targeting of desmoglein 1 in exfoliative toxin-mediated disease",

abstract = "Exfoliative toxin (ET) is secreted by Staphylococcus aureus and has long been known to cause localized or widespread epidermal blistering in humans termed bullous impetigo or staphylococcal scalded-skin syndrome, respectively. While initial hypotheses suggested that ET was a superantigen, sequence and crystallographic analysis characterized the toxin as a serine protease. More recent work determined that ET cleaves a desmosomal cadherin, desmoglein (Dsg)1. This discovery explained the mechanism of toxin-induced blistering, since Dsg1 proteolysis compromises desmosomes, which link keratinocytes and support epidermal integrity. Here, we review clinical findings in ET-mediated disease, the characterization of ET, the molecular pathogenesis of bullous impetigo/staphylococcal scalded-skin syndrome, the structure and function of Dsg1, and current and potential treatments of ET-mediated disease.",

keywords = "Staphylococcus aureus, bullous impetigo, desmoglein, desmosomal cadherin, desmosome, exfoliative toxin, staphylococcal scalded-skin syndrome",

author = "Simpson, {Cory L.} and Green, {Kathleen J.} and Spiro Getsios",

note = "Funding Information: Diseases (NIH R01 AR041836) and by an endowment from the Joseph L Mayberry Foundation. Spiro Getsios is supported by a Career Development Award from the Dermatology Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Funding Information: Cory L Simpson is supported by a Kirschstein National Research Service Award from the National Institute of Environmental Health Sciences (NIH F30 ES14990), a Presidential Fellowship from Northwestern University and a Malkin Family Scholarship from the Robert H Lurie Comprehensive Cancer Center of Northwestern University. Kathleen J Green is supported by research grants from the National Institute of Arthritis and Musculoskeletal and Skin",

year = "2010",

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doi = "10.1586/edm.10.62",

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AB - Exfoliative toxin (ET) is secreted by Staphylococcus aureus and has long been known to cause localized or widespread epidermal blistering in humans termed bullous impetigo or staphylococcal scalded-skin syndrome, respectively. While initial hypotheses suggested that ET was a superantigen, sequence and crystallographic analysis characterized the toxin as a serine protease. More recent work determined that ET cleaves a desmosomal cadherin, desmoglein (Dsg)1. This discovery explained the mechanism of toxin-induced blistering, since Dsg1 proteolysis compromises desmosomes, which link keratinocytes and support epidermal integrity. Here, we review clinical findings in ET-mediated disease, the characterization of ET, the molecular pathogenesis of bullous impetigo/staphylococcal scalded-skin syndrome, the structure and function of Dsg1, and current and potential treatments of ET-mediated disease.

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Targeting of desmoglein 1 in exfoliative toxin-mediated disease

Abstract

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