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

Williams, Michael R.; Cau, Laura; Wang, Yichen; Kaul, Drishti; Sanford, James A.; Zaramela, Livia S.; Khalil, Shadi; Butcher, A.; Zengler, Karsten; Horswill, Alexander R.; Dupont, Christopher L.; Hovnanian, Alain; Gallo, Richard L.

doi:10.1016/j.celrep.2020.02.021

Cited by 70 publications

(90 citation statements)

References 68 publications

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“…Our results show that the nonlesional skin of NS patients, although exhibiting a severe skin phenotype, including strong erythema, and several major pathophysiological commonalities with AD patients such as atopic manifestations (Malik K et al, 2019;Paller AS et al, 2017), is not over-colonized with Staphylococcus aureus, albeit the detection of the bacterium by quantitative PCR in two NS patients (Table S3). William et al recently showed, in six NS patients with ages ranging between 12-47 years old, increasing amounts of Staphylococcus aureus according to disease severity but regardless of skin lesions when compared to healthy controls (Williams MR et al, 2020). In NS patients with absent Staphylococcus aureus, Staphylococcus epidermidis predominated (Williams MR et al, 2020), hereby confirming our data.…”

Section: Recent Work Has Demonstrated That Colonization Of the Skin Bsupporting

confidence: 91%

“…William et al recently showed, in six NS patients with ages ranging between 12-47 years old, increasing amounts of Staphylococcus aureus according to disease severity but regardless of skin lesions when compared to healthy controls (Williams MR et al, 2020). In NS patients with absent Staphylococcus aureus, Staphylococcus epidermidis predominated (Williams MR et al, 2020), hereby confirming our data. Thus, these results emphasize that atopic manifestations are probably not linked to the expansion of Staphylococcus aureus and vice versa.…”

Section: Recent Work Has Demonstrated That Colonization Of the Skin Bsupporting

confidence: 91%

“…The bacterial skin microbiota of patients with NS has been recently studied (Williams MR et al, 2020). Moreover, most studies have been carried out in patients with severe AD, thus little is known on patients with milder disease.…”

Section: Introductionmentioning

confidence: 99%

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Initial Evidence of Distinguishable Bacterial and Fungal Dysbiosis in the Skin of Patients with Atopic Dermatitis or Netherton Syndrome

Moosbrugger‐Martinz

Hackl

Gruber

et al. 2021

Journal of Investigative Dermatology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Recent Work Has Demonstrated That Colonization Of the Skin Bsupporting

confidence: 91%

Section: Recent Work Has Demonstrated That Colonization Of the Skin Bsupporting

confidence: 91%

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Initial Evidence of Distinguishable Bacterial and Fungal Dysbiosis in the Skin of Patients with Atopic Dermatitis or Netherton Syndrome

Moosbrugger‐Martinz

Hackl

Gruber

et al. 2021

Journal of Investigative Dermatology

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“…These mechanisms highlight potential reasons why S. epidermidis is prone to cause device-associated infections and is the most common microbe associated with such (Zheng et al, 2018). Recently, the S. epidermidis protease EcpA was identified as a factor contributing to tissue destruction and inflammation in the monogenetic skin disorder Netherton syndrome (Williams et al, 2020), highlighting how host-dependent interactions with the resident skin microbiota can impact disease severity. Malassezia Malassezia are the most abundant fungi found on human skin (Findley et al, 2013).…”

Section: Staphylococcus Epidermidis: a Model Commensal To Probe Homeomentioning

confidence: 99%

The Skin Microbiota: Balancing Risk and Reward

Flowers

Grice

2020

Cell Host & Microbe

140

110

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The skin microbiome is an ecosystem comprised of a multitude of microbial species interacting with their surroundings, including other microbes and host epithelial and immune cells. These interactions are the basis of important roles within the skin microbiome that provide benefit to the host, boosting multiple aspects of barrier function, a critical function of this essential organ. However, with reward always comes risk; resident skin microbes function in a context-dependent manner, set on the backdrop of a dynamic host and microbial milieu. Here, we discuss the reward of hosting a microbial ecosystem on the skin, including protection from pathogens and tuning of the skin microenvironment. We also give consideration to how these skin residents, often termed ''commensals'' can cause disorder, damage, and promote skin disease.

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“…Recently, the cysteine protease EcpA was identified as a key mediator of S. epidermidisinduced AD barrier degradation [8,21]. Underscoring the importance of strain-level diversity, EcpA is present in all S. epidermidis strains but only seems to be expressed by a subset [8].…”

Section: Costs Of S Epidermidis Skin Colonizationmentioning

confidence: 99%

Staphylococcus epidermidis—Skin friend or foe?

2020

Self Cite

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Author summary Our skin is our first line of defense against environmental and pathogenic challenges. It is densely populated by a flora of bacteria, fungi, and viruses that normally interact with each other and with our immune system to promote skin health and homeostasis. Staphylococcus epidermidis is one of the most abundant bacterial colonizers of healthy human skin. While the field has historically assumed that all S . epidermidis isolates behave similarly, emerging evidence suggests that colonization by specific strains of S . epidermidis can either help or hurt the skin barrier depending on the context. In this short review, we discuss what is currently understood about S . epidermidis strain-level diversity and evaluate costs and benefits of S . epidermidis skin colonization. We challenge the current dogma that “all S . epidermidis strains behave equally” and posit that behavior is in fact highly context and strain dependent. Finally, in light of current proposals to use skin commensals as nonantibiotic treatments for acute or chronic skin diseases, we conclude that more work is urgently needed to fully understand the pathogenic and protective roles of commensals before we use them therapeutically.

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

Cited by 70 publications

References 68 publications

Initial Evidence of Distinguishable Bacterial and Fungal Dysbiosis in the Skin of Patients with Atopic Dermatitis or Netherton Syndrome

Initial Evidence of Distinguishable Bacterial and Fungal Dysbiosis in the Skin of Patients with Atopic Dermatitis or Netherton Syndrome

The Skin Microbiota: Balancing Risk and Reward

Staphylococcus epidermidis—Skin friend or foe?

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