Lysterases as first-in-class prophylactic topical antimicrobials to prevent postsurgical shoulder infections

由于老龄化，重建和替换关节的整形外科手术的需求越来越大 人口以及材料和技术的改进。然而，术后感染是 也越来越令人担忧，而且很难治疗，通常需要重新手术，从而增加了 病人的痛苦和医疗费用。这个问题在肩关节成形术中尤为严重， 强健的无菌方案在预防由枯草杆菌引起的感染方面无效 (前丙酸杆菌)痤疮，一种富含皮脂的机会性病原体 在肩部发现大量的毛囊。Demalytica正在开发一流的 针对病原菌而不影响健康微生物区系的抗菌剂。一部小说和 不同种类的分枝杆菌噬菌体编码的裂解酶可以选择性地、快速地裂解C. 粉刺，粉刺的细菌罪魁祸首。Demalytica正在开发这些裂解酶作为选择性 可以穿透皮脂腺毛囊的局部抗菌剂作为治疗痤疮的靶点 产品简介类似于用于预防肩关节置换术后感染的产品。我们 建议获得概念验证数据，用于筛选不同的裂解酶 能够杀死从肩部手术中获得的广泛的痤疮念珠菌临床分离株 已经被完全测序并进行了分子特征分析。拟议研究的成功将使 一项全面的筛选，为合适的候选人进行临床前开发，成为第一个 预防肩关节置换术感染的预防性抗菌药物 未得到满足的医疗需求。

Orthopedic surgeries to reconstruct and replace joints are increasingly in demand due to an aging population and improvements in materials and techniques. However, postsurgical infections are also of increasing concerns and are difficult to treat, often requiring revision surgeries that add to patient suffering and medical costs. This problem is particularly acute in shoulder arthroplasty, where robust aseptic protocols are not effective in preventing infections due to Cutibacterium (formerly Propionibacterium) acnes, an opportunistic pathogen enriched in sebum-rich sebaceous follicles that are found in abundance in the shoulder area. Dermalytica is developing first-in-class antimicrobials that target pathogenic bacteria without impacting healthy microbiota. A novel and diverse class of mycobacteriophage-encoded lytic enzymes can selectively and rapidly lyse C. acnes, the bacterial culprit in acne. Dermalytica is developing these lytic enzymes as selective topical antimicrobials that can penetrate sebaceous follicles as acne treatments, and the target product profile is similar to that for prevention of shoulder arthroplasty postsurgical infections. We propose to obtain proof-of-concept data on screening a panel of diverse lytic enzymes for their ability to kill a broad range of C. acnes clinical isolates obtained from shoulder surgeries that have been fully sequenced and molecularly characterized. Success in the proposed studies will enable a comprehensive screen for suitable candidates to undergo preclinical development as a first-in- class prophylactic antimicrobial to prevent shoulder arthroplasty infections and address this acute unmet medical need.