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

 描述(申请人提供)：痤疮是一种常见的皮肤病，特别是在青少年中，由于抗药性细菌的增加和当前治疗的显著副作用，有大量未得到满足的医疗需求。R型细菌素，或“收缩纳米管”(CNTs)，是由某些细菌释放的杀菌蛋白质，以赋予相对于相关菌株或其他物种的竞争优势。碳纳米管中的受体结合蛋白提供靶向特异性，与收缩支架协同工作，刺穿靶细胞，去极化细胞膜，导致离子泄漏，最终细胞死亡。改变受体结合蛋白可以将新型杂化碳纳米管重定向到所选择的目标细菌。我们将与AvidBiotics合作，利用他们的CNT平台将痤疮假单胞菌(与痤疮相关的主要机会性病原体)的受体结合区域工程到来自艰难梭菌等革兰氏阳性细菌的CNTs的收缩结构支架上。因此，我们的目标是创造新型的杂交碳纳米管，只攻击痤疮疫霉。这项概念验证提案的成功将导致这些抗微生物蛋白的进一步发展，使其成为优于目前治疗方法的有效痤疮疗法。

 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.