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

描述（由申请人提供）：人体皮肤微生物群复杂且动态。它通过与宿主免疫系统相互作用在防御病原体方面发挥重要作用。为了了解皮肤微生物群落的动态及其扰动对人类健康的影响，我们建议研究主要皮肤真菌痤疮丙酸杆菌及其在毛囊皮脂腺单位（毛囊）中的种群动态。与毛囊皮脂腺单位相关的疾病之一是痤疮。 痤疮是最常见的皮肤病之一。虽然其病因仍需确定，但已提出细菌因素在疾病的发展中。事实上，针对痤疮丙酸杆菌的抗生素治疗已经成为30多年来的主要治疗方法。 我们的初步研究表明，microcomedone是一种专门的皮肤隔间，痤疮产生，具有易于处理的微生物组，具有单一的优势物种，P.痤疮。该系统提供了一个独特的优势，允许在亚种/种群水平上深入分析人类微生物组及其动态。以前，通过16 S rDNA分析，我们发现某些痤疮丙酸杆菌核糖型在痤疮中高度富集，相反，某些核糖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了解微生物群落与人类健康和疾病之间的相关性提供了希望。 在这个项目中，我们计划从三个方向研究毛囊皮脂腺单位中微生物组的动态。首先，我们计划定义微粉刺中痤疮丙酸杆菌的种群结构和动态，并检查它们在健康和痤疮方面是否不同。其次，我们计划确定痤疮丙酸杆菌和痤疮丙酸杆菌之间是否存在捕食者-猎物种群动态，以及健康和痤疮之间的动态是否不同。第三，我们将通过微生物群和宿主的转录谱来研究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丙酸杆菌及其在健康个体和痤疮患者的毛囊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。这项研究的结果将解决我们对皮肤微生物组的认识中的一个根本性空白，并可能导致进一步的研究，以开发治疗、预防和管理这种疾病的创新临床方法。 公共卫生相关性：人类皮肤提供了抵御病原体的第一道防线。该项目的目标是调查人类皮肤表面下的微生物群落的动态及其与痤疮的关系，痤疮是一种影响1700万美国人的常见皮肤病;超过80%的人年龄在12-24岁之间。该项目的成功可能会导致开发新的有效的治疗痤疮的治疗策略。

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. PUBLIC HEALTH RELEVANCE: Human skin provides the first line of defense against pathogens. The goal of this project is to investigate the dynamics of the microbial community residing underneath the surface of human skin and its association with acne, a common skin disease affecting 17 million Americans; more than 80% of the people of age 12-24. Success in this project may lead to the development of new effective therapeutic strategies for treatment of acne.