Deriving P. acnes Bacteriophages from Skin for Acne Therapy

描述（由申请人提供）：本提案的长期目标是开发一种有效的基于噬菌体的抗微生物疗法，用于治疗痤疮，靶向痤疮丙酸杆菌，该细菌有助于皮肤病痤疮的发病机制。我们假设痤疮丙酸杆菌噬菌体和/或其部分可被鉴定为具有广泛的抗痤疮丙酸杆菌活性。这些痤疮丙酸杆菌噬菌体的关键生物学特征的鉴定将为操纵和修饰噬菌体及其溶素以开发高度特异性的痤疮治疗提供必要的信息。第一个目标将是确定痤疮患者和正常供体皮肤来源的痤疮丙酸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。一个新的方面将是开发用于工程化痤疮丙酸杆菌噬菌体以优化其宿主范围和裂解活性的系统。第二个目标将是阐明噬菌体裂解痤疮丙酸杆菌的机制，通过克隆、表达、纯化痤疮丙酸杆菌赖氨酸蛋白，随后测试它们对痤疮丙酸杆菌临床分离株的生物化学活性和抗菌活性。总之，这些研究将为来自皮肤的噬菌体感染和裂解痤疮丙酸杆菌的机制提供新的见解，这些信息可以用于开发用于治疗痤疮的基于噬菌体的疗法。 公共卫生相关性：导致痤疮发病的细菌可能受到生活在人类皮肤中的病毒的攻击。我们建议了解这些病毒杀死痤疮细菌的机制，以开发新的疗法，克服抗生素耐药细菌的出现。

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.