Deriving P. acnes Bacteriophages from Skin for Acne Therapy

描述（由申请人提供）：本申请的长期目标是开发一种有效的基于噬菌体的痤疮治疗药物，靶向痤疮丙酸杆菌，这种细菌有助于皮肤疾病痤疮的发病机制。我们假设痤疮P.噬菌体和/或它们的部分可以被鉴定为具有广泛的抗p。曼秀雷敦的活动。识别这些痤疮P.噬菌体的关键生物学特征将为操纵和修饰噬菌体及其溶酶提供必要的信息，以开发高度特异性的痤疮治疗方法。第一个目标将是确定痤疮患者和正常供体皮肤中痤疮假单胞杆菌噬菌体在宿主范围裂解模式和相关基因组差异方面的多样性。一个新的方向将是开发一个工程系统的噬菌体，以优化其宿主范围和裂解活性。第二个目标将是阐明噬菌体裂解痤疮假单胞杆菌的机制，通过克隆、表达、纯化痤疮假单胞杆菌赖氨酸蛋白，随后测试其生化活性和对痤疮假单胞杆菌临床分离株的抗菌活性。总之，这些研究将为来自皮肤的噬菌体感染和裂解痤疮P.的机制提供新的见解，这些信息可以用于开发基于噬菌体的痤疮治疗方法。

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to develop an effective phage-based antimicrobial therapy for the treatment of acne, targeting Propionibacterium acnes, the bacterium that contributes to the pathogenesis of the skin disease acne. We hypothesize that P. acnes bacteriophages, and/or their parts, can be identified as having a broad range of anti-P. acnes activity. Identification of the key biological features of these P. acnes bacteriophages will provide the necessary information to manipulate and modify the phage and its lysins for developing a highly specific acne therapy. The first goal will be to determine the diversity of P. acnes bacteriophages derived from skin of acne patients and normal donors in terms of the pattern of host range lysis and relevant genome differences. A novel aspect will be to develop a system for engineering P. acnes phage to optimize their host range and lytic activity. The second goal will be to elucidate the mechanisms by which bacteriophage lyse P. acnes, by cloning, expressing, purifying P. acnes lysine proteins, subsequently testing their biochemical activity and anti-bacterial activity against P. acnes clinical isolates. Together, these studies will provide new insight into the mechanisms by which bacteriophage derived from skin infect and lyse P. acnes information which can be leveraged towards developing a phage-based therapy for the treatment of acne. PUBLIC HEALTH RELEVANCE: The bacterium that contributes to the pathogenesis of acne can be attacked by viruses that live in human skin. We propose to learn about the mechanisms by which these viruses kill the acne bacteria in order to develop new therapies, to overcome the emergence of antibiotic resistant bacteria.