Department of Dermatology, University of California San Diego, San Diego, Calif; R&D Department, SILAB, Brive, France.
Department of Dermatology, University of California San Diego, San Diego, Calif.
J Allergy Clin Immunol. 2021 Mar;147(3):955-966.e16. doi: 10.1016/j.jaci.2020.06.024. Epub 2020 Jul 4.
Staphylococcus aureus and Staphylococcus epidermidis are the most abundant bacteria found on the skin of patients with atopic dermatitis (AD). S aureus is known to exacerbate AD, whereas S epidermidis has been considered a beneficial commensal organism.
In this study, we hypothesized that S epidermidis could promote skin damage in AD by the production of a protease that damages the epidermal barrier.
The protease activity of S epidermidis isolates was compared with that of other staphylococcal species. The capacity of S epidermidis to degrade the barrier and induce inflammation was examined by using human keratinocyte tissue culture and mouse models. Skin swabs from atopic and healthy adult subjects were analyzed for the presence of S epidermidis genomic DNA and mRNA.
S epidermidis strains were observed to produce strong cysteine protease activity when grown at high density. The enzyme responsible for this activity was identified as EcpA, a cysteine protease under quorum sensing control. EcpA was shown to degrade desmoglein-1 and LL-37 in vitro, disrupt the physical barrier, and induce skin inflammation in mice. The abundance of S epidermidis and expression of ecpA mRNA were increased on the skin of some patients with AD, and this correlated with disease severity. Another commensal skin bacterial species, Staphylococcus hominis, can inhibit EcpA production by S epidermidis.
S epidermidis has commonly been regarded as a beneficial skin microbe, whereas S aureus has been considered deleterious. This study suggests that the overabundance of S epidermidis found on some atopic patients can act similarly to S aureus and damage the skin by expression of a cysteine protease.
金黄色葡萄球菌和表皮葡萄球菌是特应性皮炎(AD)患者皮肤中最丰富的细菌。已知金黄色葡萄球菌会加重 AD,而表皮葡萄球菌被认为是有益的共生体。
本研究假设表皮葡萄球菌可以通过产生破坏表皮屏障的蛋白酶来促进 AD 皮肤损伤。
比较了表皮葡萄球菌分离株的蛋白酶活性与其他葡萄球菌种属的蛋白酶活性。通过人角质形成细胞组织培养和小鼠模型,研究了表皮葡萄球菌降解屏障和诱导炎症的能力。分析了特应性皮炎和健康成年受试者的皮肤拭子中表皮葡萄球菌基因组 DNA 和 mRNA 的存在情况。
当表皮葡萄球菌在高密度下生长时,观察到其产生强烈的半胱氨酸蛋白酶活性。负责这种活性的酶被鉴定为 EcpA,一种受群体感应控制的半胱氨酸蛋白酶。EcpA 被证明可以在体外降解桥粒芯糖蛋白 1 和 LL-37,破坏物理屏障,并在小鼠中诱导皮肤炎症。一些 AD 患者的皮肤表皮葡萄球菌丰度和 ecpA mRNA 表达增加,且与疾病严重程度相关。另一种共生皮肤细菌物种,人葡萄球菌,可抑制表皮葡萄球菌中 EcpA 的产生。
表皮葡萄球菌通常被认为是有益的皮肤微生物,而金黄色葡萄球菌则被认为是有害的。本研究表明,一些特应性皮炎患者皮肤中过度生长的表皮葡萄球菌可以通过表达半胱氨酸蛋白酶,类似于金黄色葡萄球菌,从而损害皮肤。