Anti-biofilm activity of white horehound extract in catheter-associated infection

描述（由申请方提供）：金黄色葡萄球菌是所有细菌病原体中最突出的一种。抗药性的不断出现，加上其产生毒力因子和生物膜的能力，导致社区和医院环境中的发病率和死亡率不断增加。S.金黄色葡萄球菌极难根除，并且是令人厌烦的寄生虫感染源。生物膜赋予抗微生物疗法增加的抗性，并且存在对开发生物膜疗法的明确需求。本提案的实验重点是评估从白色胡枝子（Marrubium vulgare L.，用于治疗生物膜相关的葡萄球菌感染。白色薄荷是一种原产于地中海的野生草本薄荷。它是意大利南部补充和替代医学（CAM）框架内使用的最重要的药用植物之一。特别地，该植物的提取物局部应用于治疗几种类型的皮肤和软组织感染，其中许多与葡萄球菌感染有关。我已经证实，白色白首乌的粗乙醇提取物在破坏已形成的葡萄球菌生物膜方面表现出显著的活性。该建议的实验部分分为四个目的：1）从白色热声中分离和分离生物活性化合物; 2）评估白色热声化合物在葡萄球菌生物膜背景下的体外功效; 3）评估活性化合物的体外细胞毒性;和4）使用导管相关葡萄球菌生物膜感染的鼠模型评估活性化合物的体内预防和治疗功效。 这些目标将与生物测定指导的分馏技术，其中植物化学方法（机制柱，HPLC和LC/MS）将结合在体外生物膜模型来解决。在开始动物研究之前，将评估活性化合物的细胞毒性。将使用鼠模型来评估这些化合物的体内预防能力和治疗功效。我相信，这些实验将最终导致新的治疗药物的预防和治疗葡萄球菌导管相关的生物膜感染的识别。 公共卫生相关性：金黄色葡萄球菌引起毁灭性的感染，目前抗葡萄球菌药物库不足。该提案旨在研究一种流行的基于植物的传统药物，用于预防和治疗生物膜感染的潜在治疗应用。

DESCRIPTION (provided by applicant): Staphylococcus aureus is one of the most prominent of all bacterial pathogens. The continued emergence of drug resistance combined with its ability to produce virulence factors and biofilms has lead to increasing morbidity and mortality in both community and hospital settings. Biofilms produced by S. aureus are extremely difficult to eradicate and are the wearisome source of recalcitrant infection. Biofilms confer increased resistance to antimicrobial therapy and there is a clear need for the development of hovel antibiofilm therapies. The experimental focus of this proposal is to assess the potential of natural products extracted from white horehound (Marrubium vulgare L., Lamiaceae) for the treatment of biofilm-associated staphylococcal infection. White horehound is a wild herbaceous mint native to the Mediterranean. It is one of the most important medicinal plants used within the complementary and alternative medicine (CAM) framework of southern Italy. In particular, decoctions of the plant are topically applied for the treatment of several types of skin and soft tissue infection, many of which are related to staphylococcal infection. I have already established that crude ethanolic extracts of white horehound roots demonstrate remarkable activity in the disruption of established staphylococcal biofilms. The experimental component of this proposal is divided into four aims: 1) to fractionate and isolate bioactive compounds from white horehound; 2) to assess the in vitro efficacy of white horehound compounds in the context of staphylococcal biofilms; 3) to assess the in vitro cytotoxicity of active compounds; and 4) to assess the in vivo prophylactic and therapeutic efficacy of active compound(s) using murine models for catheter-associated staphylococcal biofilm infection. These aims will be addressed with bioassay-guided fractionation techniques, in which phytochemical methods (mechanism columns, HPLC, and LC/MS) will be combined with in vitro biofilm models. The cytotoxicity of active compounds will be assessed before the initiation of animal studies. A murine model will be used to assess the prophylactic capacity and therapeutic efficacy of these compounds in vivo. I believe that these experiments will ultimately lead to the identification of novel therapeutic agents for the prevention and treatment of staphylococcal catheter-associated biofilm infection. PUBLIC HEALTH RELEVANCE: Staphylococcus aureus causes devastating infections, and the current repertoire of antistaphylococcal drugs is insufficient. This proposal is aimed at investigating a popular plant-based traditional medicine for potential therapeutic applications in the prevention and treatment of biofilm infection.