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

莱斯特酶作为一流的预防性局部抗菌剂，可预防术后肩部感染

基本信息

批准号：
10080363
负责人：
James K. Wang
金额：
$ 25.86万
依托单位：
DERMALYTICA, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-14 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10080363
关键词：
Acne Acute Address Adopted Age Antibiotic Resistance Area Bacteria Bacteriophages Biological Assay Budgets Cells Characteristics Clinical Collaborations Collection Cosmetics Data Dermatologic Development Diagnosis Digit structure Family Family member Future Gender Genetic Variation Genomics Implant Incidence Infection Infection prevention Joints Knowledge LytA enzyme Measures Medical Medical Care Costs Methods Microbial Biofilms Molecular Mycobacteriophages Operative Surgical Procedures Orthopedic Surgery procedures Orthopedics Outcome Patients Penetration Phase Phylogenetic Analysis Prevention Production Propionibacterium Propionibacterium acnes Protocols documentation Replacement Arthroplasty Risk Sebum Shoulder Site Skin Small Business Innovation Research Grant Surgeon Surgical incisions Techniques Technology Testing Time TimeLine Topical Antibiotic Universities Washington aging population antimicrobial genome analysis genome sequencing implantable device medical schools microbiota novel pathogen pathogenic bacteria phase 2 study preclinical development prevent prophylactic research clinical testing screening success whole genome

项目摘要

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.

由于老化，骨科手术重建和更换关节的需求越来越多人口和材料和技术的改进。但是，术后感染是同样越来越关注并且难以治疗，通常需要修订手术病人痛苦和医疗费用。这个问题在肩关节置换术中尤其急切，强大的无菌方案无效地预防造成的感染（以前是丙酸杆菌）痤疮，这是一种富含皮脂富含皮脂的机会性病原体在肩部区域中发现丰富的卵泡。 Dermalytica正在发展一流的靶向致病细菌而不会影响健康微生物群的抗菌素。小说和多种类分枝杆菌编码的裂解酶可以选择和快速地裂解C。痤疮，痤疮的细菌罪魁祸首。 Dermalytica正在开发这些裂解酶作为选择性可以穿透皮脂腺卵泡作为痤疮的局部抗菌剂，靶标产品概况与预防外科术后感染的肩关节置换术相似。我们建议获取有关筛选一组不同裂解酶的概念证明数据杀死从具有已完全测序并分子表征。拟议研究中的成功将使综合屏幕，适合合适的候选人，以进行临床前发展类预防性抗菌抗菌，以防止肩关节置换术感染并解决此急性未满足的医疗需求。