Targeted Antimicrobial Treatment of Acne Vulgaris by Engineered High Molecular Weight Contractile Nanotubes

工程化高分子量收缩纳米管对寻常痤疮进行靶向抗菌治疗

• 批准号: 8980303
• 负责人: James K. Wang
• 金额: $ 22.5万
• 依托单位: DERMALYTICA, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2016-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8980303
• 关键词: Acne; Acne Vulgaris; Acute; Address; Adverse effects; Affect; Age-Years; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotic Resistance; Antibiotics; Bacteria; Bacteriocin Typing; Bacteriophages; Binding; Binding Proteins; Cell Death; Cell surface; Cells; Clinical; Clinical Research; Clostridium difficile; Collaborations; Communicable Diseases; Cutaneous; Dermatology; Development; Engineered Gene; Engineering; Escherichia coli O157:H7; Extravasation; Face; Fiber; Food Safety; Future; Generations; Genes; Genetic Engineering; Goals; Gram-Positive Bacteria; Host resistance; Hybrids; In Vitro; Incidence; Investigation; Ions; Lead; Link; Listeria; Medical; Membrane; Microbiology; Molecular Weight; Nanotubes; Nosocomial Infections; Patients; Phase; Play; Propionibacterium acnes; Proteins; Pseudomonas aeruginosa; Puncture procedure; Reporting; Resistance; Risk; Role; Scientist; Severities; Skin; Small Business Innovation Research Grant; Specific qualifier value; Specificity; Tail; Technology; Teenagers; Testing; Therapeutic; Validation; Work; Yersinia pestis; antimicrobial; bactericide; cohort; effective therapy; foodborne; killings; new technology; novel; novel strategies; pathogen; pathogenic bacteria; pre-clinical; preclinical study; prevent; public health relevance; receptor binding; resistant strain; scaffold; success

 DESCRIPTION (provided by applicant): Acne is a common dermatological condition, particularly amongst teenagers, with a large unmet medical need because of the rise of antibiotic-resistant bacteria and the significant side effects of current treatments. R-type bacteriocins, or "contractile nanotubes" (CNTs), are bactericidal proteins released by certain bacteria to confer a competitive advantage over related strains or other species. The receptor-binding protein in a CNT provides target specificity, working in concert with the contractile scaffold to puncture the target cell, depolarizing the membrane, causing ion leakage and ultimately cell death. Altering the receptor-binding protein can retarget the novel hybrid CNT to the target bacteria of choice. We will collaborate with AvidBiotics to utilize their CNT platform t engineer the receptor-binding domains specific for P. acnes, the primary opportunistic pathogen causally linked to acne, onto the contractile structural scaffolds of CNTs derived from Gram-positive bacteria such as C. difficile. We therefore aim to create novel hybrid CNTs that would only attack P. acnes. Success in this proof-of-concept proposal will lead to further development of these antimicrobial proteins as effective acne therapeutics superior to current treatments.

 描述（由适用提供）：痤疮是一种常见的皮肤病条件，尤其是在青少年中，由于抗生素耐药细菌的兴起和当前治疗的显着副作用，其未满足医疗需求。 R型杆菌蛋白或“收缩纳米管”（CNTS）是某些细菌释放的细菌蛋白，以赋予相关菌株或其他物种的竞争优势。 CNT中的受体结合蛋白提供了靶标特异性，并与收缩支架共同使用，以刺穿目标细胞，使膜取消膜，导致离子泄漏并最终导致细胞死亡。改变受体结合蛋白可以将新型杂种CNT重新定位到选择的靶细菌。我们将与Avidbiotics合作利用其CNT平台T工程师The受体结合域特有的针对痤疮的受体结合域（偶尔与痤疮相关的主要机会性病原体）上的CNT的收缩结构支架，这些结构性脚手架是从革兰氏阳性细菌（例如艰难梭菌）（例如艰难梭菌）衍生而来的。因此，我们旨在创建一种只会攻击痤疮痤疮的新型混合CNT。在概念验证的建议中的成功将导致这些抗菌蛋白作为优于当前治疗的有效痤疮疗法的进一步发展。