Adhesion of Staphylococcus aureus to Corneocytes from Atopic Dermatitis Patients Is Controlled by Natural Moisturizing Factor Levels.
Adhesion of Staphylococcus aureus to Corneocytes from Atopic Dermatitis Patients Is Controlled by Natural Moisturizing Factor Levels.
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DOI：
10.1128/mbio.01184-18
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发表时间：
2018-08-14
期刊：
影响因子：
6.4
通讯作者：
Dufrêne YF
中科院分区：
文献类型：
--
作者：
Feuillie C;Vitry P;McAleer MA;Kezic S;Irvine AD;Geoghegan JA;Dufrêne YF
细菌病原体金黄色葡萄球菌在特应性皮炎 (AD) 中发挥着重要作用，特应性皮炎是一种主要影响儿童的慢性疾病。金黄色葡萄球菌在 AD 患者皮肤上的定殖会加剧疾病，但细菌与皮肤粘附相互作用的分子决定因素却知之甚少。具体来说，角质层中天然保湿因子 (NMF) 水平的降低已被证明与更严重的 AD 症状相关，但这是否与金黄色葡萄球菌粘附直接相关仍然是一个悬而未决的问题。在这里，我们证明了 AD 皮肤中 NMF 表达与细菌粘附强度之间的新关系。与高 NMF 不同，低 NMF 角质细胞被一层致密的纳米级绒毛突起覆盖。当 NMF 水平降低时，从 AD 皮肤中分离出的金黄色葡萄球菌与角质细胞的结合力更强。强结合力源自细菌粘附聚集因子 B (ClfB) 和皮肤配体之间的特定相互作用。值得注意的是，正如通过捕捉键观察到的那样，机械张力显着增强了 ClfB 介导的粘附，这表明物理压力在促进金黄色葡萄球菌在 AD 皮肤定植中发挥着作用。总的来说，我们的研究结果表明，患者 NMF 水平调节金黄色葡萄球菌 - 角质细胞粘附的强度，这是皮肤定植的第一步，并表明 ClfB 结合机制可能代表新治疗的潜在靶点。细菌与皮肤的相互作用在皮肤疾病中发挥着重要作用，但其分子细节却知之甚少。在这项研究中，我们破译了在临床上重要的特应性皮炎（AD）（也称为湿疹）中金黄色葡萄球菌粘附到皮肤角质细胞过程中发挥作用的分子力。我们发现皮肤中天然保湿因子 (NMF) 的水平与细菌-角质细胞粘附强度之间存在独特的关系。细菌粘附主要由表面蛋白聚集因子 B (ClfB) 介导，并因物理压力而增强，凸显了蛋白质机械生物学在皮肤定植中的作用。与捕获键行为类似，该机制代表了开发新型抗葡萄球菌药物的有希望的目标。
The bacterial pathogen Staphylococcus aureus plays an important role in atopic dermatitis (AD), a chronic disorder that mostly affects children. Colonization of the skin of AD patients by S. aureus exacerbates the disease, but the molecular determinants of the bacterium-skin adhesive interactions are poorly understood. Specifically, reduced levels of natural moisturizing factor (NMF) in the stratum corneum have been shown to be associated with more severe AD symptoms, but whether this is directly related to S. aureus adhesion is still an open question. Here, we demonstrate a novel relationship between NMF expression in AD skin and strength of bacterial adhesion. Low-NMF corneocytes, unlike high-NMF ones, are covered by a dense layer of nanoscale villus protrusions. S. aureus bacteria isolated from AD skin bind much more strongly to corneocytes when the NMF level is reduced. Strong binding forces originate from a specific interaction between the bacterial adhesion clumping factor B (ClfB) and skin ligands. Remarkably, mechanical tension dramatically strengthens ClfB-mediated adhesion, as observed with catch bonds, demonstrating that physical stress plays a role in promoting colonization of AD skin by S. aureus. Collectively, our findings demonstrate that patient NMF levels regulate the strength of S. aureus-corneocyte adhesion, the first step in skin colonization, and suggest that the ClfB binding mechanism could represent a potential target for new therapeutic treatments. Bacterium-skin interactions play important roles in skin disorders, yet their molecular details are poorly understood. In this study, we decipher the molecular forces at play during adhesion of Staphylococcus aureus to skin corneocytes in the clinically important context of atopic dermatitis (AD), also known as eczema. We identify a unique relationship between the level of natural moisturizing factor (NMF) in the skin and the strength of bacterium-corneocyte adhesion. Bacterial adhesion is primarily mediated by the surface protein clumping factor B (ClfB) and is enhanced by physical stress, highlighting the role of protein mechanobiology in skin colonization. Similar to a catch bond behavior, this mechanism represents a promising target for the development of novel antistaphylococcal agents.