Staphylococcus aureus commonly colonizes the skin of atopic dermatitis (AD) patients and contributes to the development and exacerbation of AD. Multiple factors are associated with colonization of AD skin by S. aureus, including the strength of S. aureus-corneocyte adhesion, deficiency of antimicrobial peptides, decreased levels of filaggrin and filaggrin degradation products, overexpressed Th2/Th17 cytokines, microbial dysbiosis and altered lipid profiles. S. aureus colonization on AD skin causes skin barrier dysfunction through virulence factors such as superantigens (toxins), enzymes and other proteins. Furthermore, colonization of AD skin by S. aureus exacerbates AD and may contribute to microbial dysbiosis, allergen sensitization, Th2/Th17 polarization, development of atopic march and food allergy in AD patients. Skin colonization of S. aureus, particularly methicillin-resistant S. aureus (MRSA), is one of the major challenges commonly encountered in the management of AD. Bleach bath, and topical or systemic antibiotics could be used to control S. aureus infection on AD skin. However, careful use of antibiotics is required to control the occurence of MRSA. Recently, various strategies, including microbiome transplant, monoclonal antibodies against virulent toxins, vaccines and recombinant phage endolysin, have been studied to control S. aureus infection on AD skin. Further advances in our understanding of S. aureus could provide us with ways to manage S. aureus colonization more effectively in AD patients.

The molecular mechanisms that underlie the detrimental effects of particulate matter (PM) on skin barrier function are poorly understood. In this study, the effects of PM _2.5 on filaggrin (FLG) and skin barrier function were investigated in vitro and in vivo. The levels of FLG degradation products, including pyrrolidone carboxylic acid, urocanic acid (UCA), and cis / trans -UCA, were significantly decreased in skin tape stripping samples of study subjects when they moved from Denver, an area with low PM _2.5 , to Seoul, an area with high PM _2.5 count. Experimentally, PM _2.5 collected in Seoul inhibited FLG, loricrin, keratin-1, desmocollin-1, and corneodesmosin but did not modulate involucrin or claudin-1 in keratinocyte cultures. Moreover, FLG protein expression was inhibited in human skin equivalents and murine skin treated with PM _2.5 . We demonstrate that this process was mediated by PM _2.5 -induced TNF-α and was aryl hydrocarbon receptor dependent. PM _2.5 exposure compromised skin barrier function, resulting in increased transepidermal water loss, and enhanced the penetration of FITC-dextran in organotypic and mouse skin. PM _2.5 -induced TNF-α caused FLG deficiency in the skin and subsequently induced skin barrier dysfunction. Compromised skin barrier due to PM _2.5 exposure may contribute to the development and the exacerbation of allergic diseases such as atopic dermatitis.

Background: Staphylococcus (S) aureus colonization is known to cause skin barrier disruption in atopic dermatitis (AD) patients. However, it has not been studied how S. aureus induces aberrant epidermal lipid composition and skin barrier dysfunction.Methods: Skin tape strips (STS) and swabs were obtained from 24 children with AD (6.0 ± 4.4 years) and 16 healthy children (7.0 ± 4.5 years). Lipidomic analysis of STS samples was performed by mass spectrometry. Skin levels of methicillin‐sensitive and methicillin‐resistant S. aureus (MSSA and MRSA) were evaluated. The effects of MSSA and MRSA were evaluated in primary human keratinocytes (HEKs) and organotypic skin cultures.Results: AD and organotypic skin colonized with MRSA significantly increased the proportion of lipid species with nonhydroxy fatty acid sphingosine ceramide with palmitic acid ([N‐16:0 NS‐CER], sphingomyelins [16:0–18:0 SM]), and lysophosphatidylcholines [16:0–18:0 LPC], but significantly reduced the proportion of corresponding very long‐chain fatty acids (VLCFAs) species (C22–28) compared to the skin without S. aureus colonization. Significantly increased transepidermal water loss (TEWL) was found in MRSA‐colonized AD skin. S. aureus indirectly through interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, IL‐6, and IL‐33 inhibited expression of fatty acid elongase enzymes (ELOVL3 and ELOVL4) in HEKs. ELOVL inhibition was more pronounced by MRSA and resulted in TEWL increase in organotypic skin.Conclusion: Aberrant skin lipid profiles and barrier dysfunction are associated with S. aureus colonization in AD patients. These effects are attributed to the inhibition of ELOVLs by S. aureus‐induced IL‐1β, TNF‐α, IL‐6, and IL‐33 seen in keratinocyte models and are more prominent in MRSA than MSSA.

Kim S, et al. Allergy Asthma Immunol Res. 2022 Sep;14(5):549-564. https://doi.org/10.4168/aair.2022.14.5.549

Kim J, et al. Allergy Asthma Immunol Res. 2023 Mar;15(2):186-200. https://doi.org/10.4168/aair.2023.15.2.186

Lee BR, et al. Immune Netw. 2021 Nov;22(2):e17. https://doi.org/10.4110/in.2022.22.e17