Department of Pediatrics, National Jewish Health, Denver, Colorado, USA.
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Allergy. 2023 May;78(5):1292-1306. doi: 10.1111/all.15640. Epub 2023 Jan 19.
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.
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.
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.
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.
金黄色葡萄球菌（S）定植已知会破坏特应性皮炎（AD）患者的皮肤屏障。然而，金黄色葡萄球菌如何诱导异常的表皮脂质组成和皮肤屏障功能障碍尚未得到研究。
从 24 名患有 AD 的儿童（6.0±4.4 岁）和 16 名健康儿童（7.0±4.5 岁）中获得皮肤胶带条（STS）和拭子。通过质谱法对 STS 样本进行脂质组学分析。评估 STS 样本中耐甲氧西林金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA）的皮肤水平。在原代人角质形成细胞（HEK）和器官型皮肤培养物中评估 MSSA 和 MRSA 的作用。
AD 和 MRSA 定植的器官型皮肤显著增加了具有非羟基脂肪酸神经酰胺的脂质种类的比例，具有棕榈酸（[N-16:0 NS-CER]，神经鞘磷脂[16:0-18:0 SM]）和溶血磷脂酰胆碱[16:0-18:0 LPC]，但与无金黄色葡萄球菌定植的皮肤相比，相应的超长链脂肪酸（VLCFA）种类（C22-28）的比例显著降低。MRSA 定植的 AD 皮肤发现明显增加的经皮水分流失（TEWL）。金黄色葡萄球菌通过白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α、IL-6 和 IL-33 间接抑制角质形成细胞中的脂肪酸延长酶（ELOVL3 和 ELOVL4）的表达。MRSA 引起的 ELOVL 抑制更为明显，并导致器官型皮肤 TEWL 增加。
异常的皮肤脂质谱和屏障功能障碍与 AD 患者的金黄色葡萄球菌定植有关。这些影响归因于金黄色葡萄球菌诱导的白细胞介素（IL）-1β、TNF-α、IL-6 和 IL-33 抑制角质形成细胞模型中的 ELOVLs，并且在 MRSA 中比 MSSA 更为明显。
