Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis.

Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis.
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DOI:
10.1126/scitranslmed.aal4651
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发表时间:
2017-07-05
影响因子:
17.1
通讯作者:
Kong HH
Kong HH
中科院分区:
医学1区
文献类型:
--
作者:
Byrd AL;Deming C;Cassidy SKB;Harrison OJ;Ng WI;Conlan S;NISC Comparative Sequencing Program;Belkaid Y;Segre JA;Kong HH

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特应性皮炎(AD;湿疹)患者的不同病程、严重程度和治疗反应突出了这种多因素疾病的复杂性。先前的研究使用传统的分型方法对培养的分离物进行分型或对细菌标记基因进行测序来研究AD患者的皮肤微生物群落。散弹枪宏基因组序列分析提供了更高的分辨率,阐明了从界到种和菌株水平多样化的多个层次的微生物群落组装。在这里,我们分析了一组儿科AD患者在整个病程中的微生物时间动态。对AD耀斑的物种水平调查显示,病情较严重的患者以金黄色葡萄球菌为主,而病情较轻的患者以表皮葡萄球菌为主。在菌株水平上,宏基因组测序分析显示,在更严重的患者中存在克隆性金黄色葡萄球菌菌株,而在所有患者中存在异质性表皮葡萄球菌菌株群落。为了研究金黄色葡萄球菌在菌株水平上的生物学效应,我们用从AD患者和对照组分离的菌株局部定殖小鼠。该皮肤定植模型显示了金黄色葡萄球菌菌株在引发AD患者皮肤炎症和免疫特征方面的特异性差异。具体而言,来自AD患者的金黄色葡萄球菌分离物具有更严重的耀斑,可诱导表皮增厚和皮肤Th2和Th17细胞扩张。整合高分辨率测序,培养和动物模型证明了葡萄球菌菌株的功能差异如何可能导致AD疾病的复杂性。
The heterogeneous course, severity, and treatment responses among patients with atopic dermatitis (AD; eczema) highlight the complexity of this multifactorial disease. Prior studies have used traditional typing methods on cultivated isolates or sequenced a bacterial marker gene to study the skin microbial communities of AD patients. Shotgun metagenomic sequence analysis provides much greater resolution, elucidating multiple levels of microbial community assembly ranging from kingdom to species and strain-level diversification. Here, we analyze microbial temporal dynamics from a cohort of pediatric AD patients sampled throughout the disease course. Species-level investigation of AD flares showed greater Staphylococcus aureus-predominance in patients with more severe disease and S. epidermidis-predominance in patients with less severe disease. At the strain-level, metagenomic sequencing analyses demonstrated clonal S. aureus strains in more severe patients and heterogeneous S. epidermidis strain communities in all patients. To investigate strain-level biological effects of S. aureus, we topically colonized mice with strains isolated from AD patients and controls. This cutaneous colonization model demonstrated S. aureus strain-specific differences in eliciting skin inflammation and immune signatures characteristic of AD patients. Specifically, S. aureus isolates from AD patients with more severe flares induced epidermal thickening and expansion of cutaneous Th2 and Th17 cells. Integrating high-resolution sequencing, culturing, and animal models demonstrated how functional differences of staphylococcal strains may contribute to the complexity of AD disease.
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