Incorporation of a biofilm dispersion autoinducer into an antimicrobial ointment for the treatment of topical wounds

项目摘要 三种生物被膜形成细菌鲍曼不动杆菌、铜绿假单胞菌和 金黄色葡萄球菌，最近被世卫组织确定为关键或高度优先的病原体，新的 迫切需要抗生素或抗微生物治疗1。我们认为无法有效地预防或治疗 一系列与生物膜有关的慢性疾病可以通过使用生物膜扩散信号作为 作为传统抗菌疗法的补充。我们实验室的研究表明，P. 铜绿假单胞菌产生一种群体感应分子，顺式-2-癸烯酸(cis-DA)，负责自动... 生物被膜细菌天然弥散反应的诱导。这种信号分子已被证明能诱导 细菌的一种生理变化，使它们从生物膜中解体并改变它们的生理。 使他们更容易受到抗生素的影响。此外，顺式-多巴胺已被证明可以诱导生物膜分散。 在广泛的革兰氏阴性和革兰氏阳性细菌以及真菌中。在这里，我们建议确定 顺式-DA能在多大程度上提高以石油凝胶为基础的软膏的抗生物被膜活性 包埋抗菌剂(多粘菌素B、杆菌肽和新霉素)。实验将检验杀戮前的 形成了单物种和多物种生物膜。在确认顺式-DA辅助治疗对 对于人角质形成细胞，我们将在体外创伤和感染皮肤模型上测试其效果。在…的最后一行 研究中，我们将在小鼠创伤模型上检验该治疗方法的有效性和安全性。我们期待着 这项工作将产生一种抗菌/抗生物膜配方，将改善目前的治疗和 预防局部创面生物被膜感染的策略。

Project Summary Three species of biofilm-forming bacteria, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus, were recently identified by WHO as critical or high priority pathogens for which new antibiotics or antimicrobial treatments are urgently needed1. We believe the inability to effectively prevent or treat a wide range of biofilm-related chronic diseases may be overcome by using a biofilm dispersal signal as an adjunctive to conventional antimicrobial therapies. Studies in our laboratory have demonstrated that P. aeruginosa produces a quorum sensing molecule, cis-2-decenoic acid (cis-DA), that is responsible for auto- induction of the native dispersion response in biofilm bacteria. This signaling molecule has been shown to induce a physiological change in bacteria, causing them to disaggregate from a biofilm and alter their physiology, rendering them more susceptible to antibiotics. Additionally, cis-DA has been shown to induce biofilm dispersion in a wide range of Gram-negative and Gram-positive bacteria, as well as fungi. Here we propose to determine the degree to which cis-DA can improve the anti-biofilm activity of a petroleum jelly-based ointment with embedded antimicrobials (polymyxin B, bacitracin and neomycin). Experiments will examine the killing of pre- formed single- and multi-species biofilms. After confirming that the cis-DA adjunctive treatment is not toxic to human keratinocytes, we will test the effects on in vitro models of wounded and infected skin. In the final line of investigation, we will examine the efficacy and safety of the treatment in murine wound model. We anticipate that this work will result in an antimicrobial/anti-biofilm formulation that will improve current treatment and prevention strategies against biofilm infections in topical wounds.