Philipp Licht, Nazzareno Dominelli, Johannes Kleemann, Stefan Pastore, Elena-Sophia Müller, Maximilian Haist, Kim Sophie Hartmann, Henner Stege, Matthias Bros, Markus Meissner, Stephan Grabbe, Ralf Heermann, Volker Mailänder
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引用次数: 0
摘要
真菌病(MF)是皮肤 T 细胞淋巴瘤(CTCL)中最常见的一种,其特点是皮肤中存在克隆性恶性 T 细胞。目前,人们对皮肤微生物组在 MF 发生和发展过程中的作用还知之甚少。我们使用枪式元基因组剖析、实时 qPCR 和 T 细胞受体测序技术,比较了 20 名早期和晚期 MF 患者的病变和非病变皮肤。此外,我们还从 MF 皮肤中分离出了金黄色葡萄球菌和其他细菌,以进行功能分析并研究金黄色葡萄球菌的毒力因子 spa。我们发现有一部分手足口病患者的皮损处存在严重的菌群失调,斑块期皮损处同时有金黄色葡萄球菌生长,而其他手足口病患者的皮损处微生物群平衡。菌群失调和金黄色葡萄球菌生长伴随着皮肤抗菌肽(AMPs)水平的异位,包括斑块衍生的金黄色葡萄球菌菌株的适应。此外,菌斑衍生的金黄色葡萄球菌菌株对抗生素的敏感性降低,毒力因子 spa 上调,这可能会激活 NF-κB 通路。值得注意的是,中耳炎病变上菌群失调的患者T细胞受体谱系受限,无事件生存率明显降低。我们的研究强调了针对金黄色葡萄球菌的微生物组调节疗法在预防 MF 进展方面的潜力。
The skin microbiome stratifies patients with cutaneous T cell lymphoma and determines event-free survival.
Mycosis fungoides (MF) is the most common entity of Cutaneous T cell lymphomas (CTCL) and is characterized by the presence of clonal malignant T cells in the skin. The role of the skin microbiome for MF development and progression are currently poorly understood. Using shotgun metagenomic profiling, real-time qPCR, and T cell receptor sequencing, we compared lesional and nonlesional skin of 20 MF patients with early and advanced MF. Additionally, we isolated Staphylococcus aureus and other bacteria from MF skin for functional profiling and to study the S. aureus virulence factor spa. We identified a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. Our study highlights the potential for microbiome-modulating treatments targeting S. aureus to prevent MF progression.
期刊介绍:
npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.