Antibacterial activity and mechanism of action of semi-synthetic cocktail formulated from the Bald's eyesalve

秃头眼药半合成鸡尾酒的抗菌活性及作用机制

• 批准号: 2590910
• 金额: --
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2590910
• 关键词: Antibacterial; activity; mechanism; action; semi

Antimicrobial-resistant infections, especially those associated with biofilms, continue to create a global health challenge due to the high mortality and economic loss associated with drug-resistant infections. Chronic wound infections and lung infections in people with cystic fibrosis both pose annual economic burdens of $281Bn and $7509Bn respectively. Prior to the discovery of antibiotics, infections were often treated with combinations of different natural products. Our lab has identified a medieval remedy called "Bald's eyesalve" which was used to treat eye infections. This remedy has shown broad-spectrum activities against planktonic and biofilm forms of wound and lung pathogens. Starting from preliminary data already obtained in our lab, our plan is to formulate a semi-synthetic cocktail comprising only the compounds that give this complex recipe its biological activity. We will narrow down the complex remedy to a set of semi-synthetic or fully synthetic mixtures of natural products, and test the ability of these cocktails to eradicate biofilms of Staphylococcus aureus and Pseudomonas aeruginosa in wound and lung biofilm models. This will allow us to formulate a final, chemically defined cocktail that could be used to treat infections. Furthermore, we will determine the mechanism of action of our cocktail against the two pathogens mentioned. We will also look to enhance the activity of our cocktail by combining it with other antimicrobials, and to assess its safety profile for therapeutic use. This project will pave way for a new approach to testing the antimicrobial activity of natural products through the combination of different bioactive compounds in their natural and synthetic forms.

由于与耐药感染相关的高死亡率和经济损失，耐药感染，特别是与生物被膜相关的感染，继续造成全球健康挑战。囊性纤维化症患者的慢性伤口感染和肺部感染每年分别造成2810亿美元和75090亿美元的经济负担。在发现抗生素之前，感染通常是用不同的天然产品组合治疗的。我们的实验室发现了一种名为“秃头眼膏”的中世纪药物，用于治疗眼部感染。这种药物对浮游生物和生物膜形式的伤口和肺部病原体显示了广泛的活性。从我们实验室已经获得的初步数据开始，我们的计划是配制一种半合成鸡尾酒，其中只包含使这一复杂配方具有生物活性的化合物。我们将把复杂的药物范围缩小到一系列半合成或全合成的天然产品混合物，并测试这些鸡尾酒在伤口和肺生物膜模型中根除金黄色葡萄球菌和铜绿假单胞菌生物膜的能力。这将使我们能够配制出最终的、化学定义的鸡尾酒，可以用于治疗感染。此外，我们将确定我们的鸡尾酒对上述两种病原体的作用机制。我们还将寻求通过将我们的鸡尾酒与其他抗菌剂结合来增强其活性，并评估其用于治疗的安全性。该项目将通过天然和合成形式的不同生物活性化合物的组合，为测试天然产品的抗菌活性铺平道路。