Real-time visualisation and modelling of biofilm inhibition by lactam

为了实现其环境目标，联合利华在天然和天然衍生产品成分方面拥有既得利益。抗菌剂和抗生物膜技术在联合利华的配方、包装和加工中作为性能活性物质或防腐剂得到应用。作为联合利华业务的核心，家庭和个人护理液体配方（如Surf、Domeirs、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。在点心和食品类别中，人们一直致力于通过生物膜产品加工和包装技术来提高产品的完整性和寿命。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性、监管和非政府组织的压力。已经评估了超过600种化学品（称为呋喃酮衍生的内酰胺类似物）的库的抗生物膜潜力，这些化学品来源于Delisea pulchra，一种通常没有细菌生物膜生长的海藻。一些变体已显示在生物膜生长和成熟期间破坏群体感应（细胞-细胞信号传导），而不诱导微生物适应。已经证明内酰胺类似物干扰群体感应，作为革兰氏阴性菌上的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-细胞串扰就开始了，其控制着从早期可逆的吸附、锚定、聚集和表面定殖到EPS分泌、生物膜的毒力和扩散的事件。到目前为止，尚未完全了解该工艺的哪个或哪些阶段受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，澄清生物和物理过程的作用至关重要。该项目旨在实时观察由联合利华的内酰胺类似物诱导的非嗜热菌的表型变化。特别是，它将通过3D可视化和建模来探索早期生物膜发展的治疗活动的全方位，探索非渗透性细胞表面结合的最早阶段对成熟生物膜结构和功能的持久影响。它将采用约克大学的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三维流场以及群体感应活动，并将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。

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.