Rational modification of lactams for improved efficacy in home care applications

除了去除污垢，家庭和个人护理配方，如洗衣剂、家用表面清洁剂、沐浴露配方和洗发水，旨在提供符合联合利华可持续生活计划（USLP）的健康和卫生效益。目前能够实现这些益处的功能性成分是化学抗菌剂，它对生物膜的功效有限，并且有导致微生物耐药性的风险。这些配方的一个关键困难是它们能够杀死在抗性更强的生物膜中形成的细菌。对600多个呋喃酮衍生内酰胺的筛选揭示了在生物膜生长和发育过程中破坏群体感应的变异，因此假设它们会减少生物膜形成的倾向。与所有早期创新技术一样，内酰胺类也面临着技术、安全和监管方面的挑战。本可行性项目旨在通过对现有主要类似物进行合理改性，解决内酰胺在液体洗涤剂配方中应用的技术障碍，如增溶性差和效率降低。衍生化的可能途径包括接枝水溶性聚合物或带电基团以获得溶解度，或接枝含内酰胺的聚合物材料以靶向递送到表面和生物膜。将建立一个大约10种新型类似物的有限文库，并探索它们的抗生物膜功效。将评估涵盖家庭和个人护理液体的一系列应用的生物技术平台的可能性。MMU将承担的工作包括内酰胺类似物的制备和测试。这将允许准确地确定内酰胺的抗菌浓度。MMU的PI和PDRA将进行结晶紫试验，以证明这些新化合物的抗生物膜活性。共聚焦显微镜将用于研究内酰胺类在静态和流动条件下对生物膜活力的影响。MMU的实验室研究也将探索生物膜的抑制作用。为了做到这一点，研究小组将使用Live/Dead系统或Bioflux类型的系统——通过可视化LasR gfp（生物信号）和POA1-LasB rfp（生物质）来完成。革兰氏阴性紫罗兰色杆菌将用于证明AHL信号抑制，通过缺乏紫色紫罗兰素的生产。最后，MMU将负责向相关学科的学者进行科学传播。这将通过在2016年6月于葡萄牙举行的国际生物膜会议上发表，以及根据该研究发表同行评议的期刊文章来实现。

Beyond removal of dirt, home and personal care formulations such as laundry detergents, household surface cleaners, body wash fomulations and shampoos aim to deliver health and hygiene benefits in line with Unilever's Sustainable Living Plan (USLP). The current functional ingredients to enable such benefits is chemical antimicrobials which have a limited efficacy on biofilms and a risk of driving microbial resistance. A key difficulty for these formulations is their ability to kill bacteria that have formed in a more resistant biofilm. The screening of a library of over 600 furanone-derived lactams has revealed variants that disrupt quorum sensing during biofilm growth and development, and hence hypothetically they will reduce the propensity for biofilm formation. As with all early stage innovation technologies, lactams face technical, safety and regulatory challenges. This feasibility project aims to address technical hurdles in the application of lactams in liquid detergent formulations such as poor solubilisation and reduced efficacy via rational modification of existing principal analogues. Possible routes of derivatisation will include grafting water soluble polymers or charged groups for solubility or grafting polymeric lactam-containing materials for targeted delivery to surfaces and biofilms. A limited library of around 10 novel analogues will be constructed and their anti-biofilm efficacy will be explored. The possibility of a biotechnology platform that covers a range of applications across home and personal care liquids will be assessed.The work that MMU will undertake involves the preparation and testing of the lactam anologues. This will allow antimicrobial concentrations of the lactams be accurately determined. The PI and PDRA at MMU will undertake crystal violet assays in order to demonstrate the anti-biofilm activity of these novel compounds. Confocal microscopy will be used to investigate the effect of the lactams on biofilm viability in static and flow conditions. The MMU laboratory research will also explore biofilm inhibition. To do this, the research team will either use the Live/Dead systems or a Bioflux type system - done by visualising LasR gfp (biosignalling) and POA1-LasB rfp (biomass). The Gram negative Chromobacterium violaceum will be used to demonstrate AHL signalling inhibition through lack of the production of the purple coloured violacein. Finally, MMU will be responsible for scientific dissemination to academics in relevant disciplines. This will be achieved by presenting at the International Biofilms conference in Portugal in June 2016, as well as through publishing peer reviewed journal articles based on the research.