Elucidating the Molecular Mechanisms of Action and Resistance of Microbes to Anti-biofilm Lactam Technology

在家庭和各种商业环境中提供卫生解决方案越来越成问题，特别是在表面不断受到微生物污染，特别是生物膜形成的挑战的情况下。这个问题通常使用包括重金属和季铵化合物的传统杀生物抗微生物剂来解决，然而这些存在环境和毒理学危害，并且可能导致抗微生物剂耐药性的出现。在自然界中，红色海藻Delisea pulchra通过产生具有抗生物膜特性的呋喃酮来避免污染和感染，并阻断参与生物膜发育的某些细菌群体感应（QS）途径。联合利华开发了一个基于这些呋喃酮结构的生物启发内酰胺库，这些结构已被证明具有抗生物膜特性和整体“绿色”特征。来自联合利华/诺丁汉先前合作的数据表明，内酰胺具有多种作用机制，并与不同细菌物种中的不同分子靶标相互作用。该项目将研究金黄色葡萄球菌和其他细菌中主要的假定内酰胺靶标，重点是阐明作用模式以及在长期暴露于特定内酰胺后是否选择内酰胺耐药性。

Delivering hygiene solutions around the home and in diverse commercial settings is increasingly problematic, particularly where surfaces are continuously challenged by microbial contamination and particularly by biofilm formation. This problem is usually addressed using traditional biocidal antimicrobials which include heavy metals and quaternary ammonium compounds, however these present environmental and toxicological hazards and may contribute to the emergence of antimicrobial resistance. In nature, the red seaweed Delisea pulchra avoids contamination and infection by producing furanones that have anti-biofilm properties and block certain bacterial quorum sensing (QS) pathways involved in biofilm development. Unilever has developed a library of bioinspired lactams based on these furanone structures that have been shown to have anti-biofilm properties and an overall 'greener' profile. Data from a previous Unilever/Nottingham collaboration suggests that lactams exhibit multiple mechanisms of action and interact with different molecular targets in different bacterial species. This project will investigate the major putative lactam target in Staphylococcus aureus and other bacteria, focussing on elucidating the mode of action and whether lactam resistance is selected following prolonged exposure to specific lactams.