Real-time visualisation and modelling of biofilm inhibition by lactam

内酰胺生物膜抑制的实时可视化和建模

• 批准号: BB/N024095/1
• 负责人: Martin Bees
• 金额: $ 6.13万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN024095%2F1
• 关键词: Real; time; visualisation; modelling; biofilm

In order to meet its environmental targets Unilever has a vested interest in natural and nature-derived product ingredients. Antimicrobials and anti-biofilm technologies find applications in Unilever's formulations, packaging, and processing either as performance actives or preservatives. At the core of Unilever's business, home and personal care liquid formulations (e.g. Surf, Domestos, Dove) aim at improving surface hygiene and freshness through biostatic and anti-biofilm actives. In refreshment and food categories there is a continuous ambition to improve the integrity and lifespan of products with biofilm-ready product processing and packaging technologies. Current microbial control ingredients are receiving increased safety, regulatory and NGO pressure due to their petrochemical profile. The anti-biofilm potential of a library of over 600 chemicals (called furanone derived lactam analogues) have been assessed that are derived from Delisea pulchra, a marine algae that typically is devoid of bacterial biofilm growth. Some variants have been shown to disrupt quorum sensing (cell-cell signalling) during biofilm growth and maturation, without inducing microbial adaptation. It has been demonstrated that lactam analogues jam quorum sensing, acting as antagonists of signal molecule receptors on gram negative bacteria. From the moment free floating cells start adsorbing reversibly on surfaces, cell-cell crosstalk is initiated that controls events from the early reversible adsorption, anchorage, aggregation and colonisation of the surface to secretion of EPS, virulence and dispersal of the biofilm. To-date it is not fully understood which stage(s) of the process are affected by the lactam analogues. In order to progress the anti-biofilm lactam analogue treatment to market, and obtain the requisite regulatory approval, it is essential that the role of biological and physical processes is clarified. This project aims to visualise in real-time phenotypic changes to non-planktonic bacteria induced by Unilever's lead lactam analogue. In particular, it will explore the full spectrum of activity of the treatment on early stage biofilm development by visualisation and modelling in 3D, exploring the very earliest stages of non-planktonic cell-surface association to lasting impact on mature biofilm structure and functionality. It will employ unique state-of-the-art holographic and imaging techniques developed by the research investigators at the University of York to measure microscopic 3D flow fields together with quorum sensing activity and, in tandem, will construct a mechanistic mathematical description of the interaction of biological and physical processes. These approaches will aim to identify the limiting factor(s) of lactam analogue biofilm inhibition and inform the design of next generation anti-biofilm technologies.

为了实现其环保目标，联合利华对天然和天然衍生产品成分拥有既得利益。抗菌剂和抗生物膜技术作为功能活性剂或防腐剂应用于联合利华的配方、包装和加工中。作为联合利华业务的核心，家庭和个人护理液体配方（例如 Surf、Domestos、Dove）旨在通过生物抑制和抗生物膜活性物质改善表面卫生和新鲜度。在茶点和食品类别中，人们一直致力于通过生物膜就绪的产品加工和包装技术来提高产品的完整性和使用寿命。目前的微生物控制成分由于其石化特性而受到越来越大的安全、监管和非政府组织压力。超过 600 种化学物质（称为呋喃酮衍生内酰胺类似物）的抗生物膜潜力已经过评估，这些化学物质源自 Delisea pulchra（一种通常不生长细菌生物膜的海洋藻类）。一些变体已被证明会在生物膜生长和成熟过程中破坏群体感应（细胞间信号传导），但不会诱导微生物适应。已证明内酰胺类似物干扰群体感应，充当革兰氏阴性细菌上信号分子受体的拮抗剂。从自由漂浮的细胞开始可逆地吸附在表面上的那一刻起，细胞间的串扰就开始了，它控制着从表面的早期可逆吸附、锚定、聚集和定植到 EPS 的分泌、生物膜的毒力和分散的事件。迄今为止，尚不完全了解该过程的哪些阶段受到内酰胺类似物的影响。为了将抗生物膜内酰胺类似物治疗推向市场并获得必要的监管批准，必须澄清生物和物理过程的作用。该项目旨在实时可视化由联合利华的先导内酰胺类似物诱导的非浮游细菌的表型变化。特别是，它将通过 3D 可视化和建模来探索治疗对早期生物膜发育的全方位活性，探索非浮游细胞表面关联的最早阶段对成熟生物膜结构和功能的持久影响。它将采用约克大学研究人员开发的独特的最先进的全息和成像技术来测量微观 3D 流场和群体感应活动，并同时构建生物和物理过程相互作用的机械数学描述。这些方法旨在确定内酰胺类似物生物膜抑制的限制因素，并为下一代抗生物膜技术的设计提供信息。