Population dynamics of P. acnes and their phages in the human skin microbiome

描述(申请人提供)：人类皮肤微生物区系是复杂和动态的。它通过与宿主免疫系统相互作用，在抵御病原体方面发挥着重要作用。为了了解皮肤微生物群落的动态及其对人类健康的影响，我们建议研究主要的皮肤共生菌痤疮丙酸杆菌及其在毛囊单位(毛囊)中的噬菌体的种群动态。与毛囊皮脂腺单位相关的疾病之一是痤疮。粉刺是最常见的皮肤病之一。虽然其病因仍需确定，但细菌因素已被认为在疾病的发展中。事实上，30多年来，针对痤疮假单胞菌的抗生素治疗一直是主要的治疗方法。我们的初步研究表明，微粉刺是一种专门的皮肤隔膜，在那里会出现粉刺，它有一个易于驯服的微生物群，只有一个优势种，即痤疮假单胞菌。这个系统提供了一个独特的优势，可以在亚种/种群水平上深入分析人类微生物群及其动态。此前，通过16S rDNA分析，我们发现某些核型痤疮杆菌高度富含痤疮，相比之下，某些核型核型在健康皮肤中过度表达。这表明，研究微生物群落的结构和动态为理解微生物群落与人类健康和疾病之间的关系提供了希望。在这个项目中，我们计划从三个方向研究毛脂单位中TH微生物群的动态。首先，我们计划确定微粉病中痤疮假单胞菌的种群结构和动态，并检查它们在健康和痤疮方面是否存在差异。其次，我们计划确定痤疮假单胞菌和痤疮假单胞菌噬菌体之间是否存在捕食者-被捕食者的种群动态，以及这种动态在健康和痤疮方面是否不同。第三，我们将通过微生物区系和宿主的转录图谱来检查微生物和宿主之间的相互作用，并确定微生物群落的变化是否会改变宿主的免疫反应。这项拟议的研究将确定痤疮假单胞菌及其噬菌体在健康人和痤疮患者的毛皮脂腺单位中的种群结构和动态，以及它们与宿主的相互作用。这项研究的发现将解决我们对皮肤微生物组知识的一个根本差距，并可能导致进一步研究开发治疗、预防和管理这种疾病的创新临床方法。

DESCRIPTION (provided by applicant): The human skin microbiota is complex and dynamic. It plays a significant role in defending against pathogens by interacting with the host immune system. To understand the dynamics of the skin microbial community and the effect on the human health upon its perturbation, we propose to study the population dynamics of a major skin commensal, Propionibacterium acnes, and its phages in pilosebaceous units (hair follicles). One of the diseases associated with pilosebaceous units is acne. Acne is one of the most common skin diseases. Although its etiology still needs to be defined, a bacterial factor has been suggested in the development of the disease. In fact, antibiotic therapy targeting P. acnes has been a mainstay treatment for more than 30 years. Our preliminary study shows that microcomedone, a specialized skin compartment where acne arises, has a tractable microbiome with a single dominant species, P. acnes. This system offers a unique advantage allowing in-depth analysis of a human microbiome and its dynamics at the subspecies/population level. Previously, by 16S rDNA analysis, we found that certain P. acnes ribotypes are highly enriched in acne, and in contrast, certain ribotype is over-represented in healthy skin. This indicates that studying the structure and dynamics of the microbial community offers promise for understanding the correlation between the microbial community and human health and disease. In this project, we plan to investigate in three directions the dynamics of th microbiome in pilosebaceous units. First, we plan to define the population structure and dynamics of P. acnes in microcomedones and examine whether they are different in health and acne. Second, we plan to determine whether predator-prey population dynamics exist between P. acnes and P. acnes phages and whether the dynamics are different in health and acne. Third, we will examine the interactions between the microbes and the host by transcriptional profiling of both the microbiota and the host and determine whether changes in the microbial community alter the host immune responses. This proposed study will define the population structure and dynamics of P. acnes and its phages in the pilosebaceous units of healthy individuals and acne patients and their interactions with the host. The findings from the study will address a fundamental gap in our knowledge of the skin microbiome and may lead to further studies for the development of innovative clinical approaches to treating, preventing and managing the disease.