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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

基本信息

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
项目类别：
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

项目摘要

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.