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（由申请人提供）：痤疮是一种常见的皮肤病，尤其是在青少年中，由于抗生素耐药细菌的增加以及当前治疗方法的显着副作用，痤疮的医疗需求尚未得到满足。 “纳米管”（CNT）是某些细菌释放的杀菌蛋白，与相关菌株或其他物种相比，CNT 中的受体结合蛋白提供了靶标特异性，协同作用。利用收缩支架刺穿靶细胞，使细胞膜去极化，导致离子泄漏并最终导致细胞死亡。我们将与 AvidBiotics 合作，利用他们的 CNT。平台将痤疮丙酸杆菌（与痤疮有因果关系的主要机会性病原体）特异的受体结合域设计到源自革兰氏阳性菌（例如痤疮丙酸杆菌）的碳纳米管的收缩结构支架上。因此，我们的目标是创造只攻击痤疮丙酸杆菌的新型混合碳纳米管，这一概念验证提案的成功将导致这些抗菌蛋白作为优于现有治疗方法的有效痤疮治疗剂的进一步发展。