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• W3201700187 abstract "Abstract Atopic Dermatitis (AD) is associated with a deficiency of skin lipids, increased populations of Staphylococcus aureus in the microbiome, and structural defects in the stratum corneum (SC), the outermost layer of human skin. However, the pathogenesis of AD is ambiguous as it is unclear whether observed changes are the result of AD or contribute to the pathogenesis of the disease. Previous studies have shown that S. aureus is capable of permeating across isolated human SC tissue when lipids are depleted to levels consistent with AD conditions. In this study, we expand upon this discovery to determine the mechanisms of bacterial penetration into the SC barrier. Specifically, we establish whether bacteria are permeating intercellularly, between corneocytes, or employing a combination pathway of both inter- and intra-cellular travel. The mechanical implications of bacterial invasion, lipid depletion, and media immersion are also evaluated using a newly developed, physiologically relevant, temperature-controlled drip chamber. Results reveal that S. aureus can be internalized by corneocytes, indicating transcellular movement through the tissue during permeation, consistent with previous theoretical models. S. aureus also degrades the mechanical integrity of human SC, particularly when the tissue is partially depleted of lipids. These observed mechanical changes are likely the cause of broken or ruptured tissue seen as exudative lesions in AD flares. This work further highlights the necessity of lipids in skin microbial barrier function. Importance Millions of people suffer from the chronic inflammatory skin disease Atopic Dermatitis (AD), whose symptoms are associated with a deficiency of skin lipids that exhibit antimicrobial functions, and increased populations of the opportunistic pathogen Staphylococcus aureus . However, the pathogenesis of AD is ambiguous, and it remains unclear if these observed changes are merely the result of AD, or contribute to the pathogenesis of the disease. In this article, we demonstrate the necessity of skin lipids in preventing S. aureus from penetrating the outermost barrier of human skin thereby causing a degradation in tissue integrity. In terms of AD, this bacterial permeation into the viable epidermis could act as an inflammatory trigger of the disease and could also explain tissue fragility and lesion formation seen with AD patients. Moreover, bacterial induced degradation could lead to increased pathways and further allergen intervention creating chronic irritation." @default.
• W3201700187 created "2021-10-11" @default.
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• W3201700187 date "2021-10-07" @default.
• W3201700187 modified "2023-09-27" @default.
• W3201700187 title "Bacterial invasion across the human skin barrier – mechanisms and ensuing tissue degradation" @default.
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• W3201700187 doi "https://doi.org/10.1101/2021.10.06.463452" @default.
• W3201700187 hasPublicationYear "2021" @default.
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