Rational modification of lactams for improved efficacy in home care applications

除了去除污垢，家用和个人护理配方，如洗衣粉、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。目前实现这种好处的功能性成分是化学抗菌剂，它们对生物被膜的疗效有限，并有导致微生物耐药性的风险。这些制剂的一个关键困难是它们能否杀死在更具耐药性的生物膜中形成的细菌。对600多个呋喃酮类内酰胺类抗生素文库的筛选发现，在生物被膜的生长和发育过程中，会扰乱群体感应的变异，因此假设它们会降低生物被膜的形成倾向。与所有早期创新技术一样，内酰胺类药物面临着技术、安全和监管方面的挑战。这一可行性项目旨在通过合理修改现有的主要类似物，解决在液体洗涤剂配方中应用内酰胺类药物的技术障碍，如增溶作用差和药效降低。可能的衍生化途径包括接枝水溶性聚合物或带电基团用于溶解，或接枝含有内酰胺的聚合物材料用于定向输送到表面和生物膜。将建立一个由大约10个新类似物组成的有限文库，并将探索它们的抗生物被膜效果。将评估生物技术平台覆盖家庭和个人护理液的一系列应用的可能性。MMU将承担的工作包括内酰胺类似物的准备和测试。这将使内酰胺类药物的抗菌浓度得到准确测定。MMU的PI和PDRA将进行结晶紫检测，以证明这些新化合物的抗生物被膜活性。共聚焦显微镜将被用来研究在静态和流动条件下内酰胺类药物对生物膜活力的影响。MMU的实验室研究还将探索生物膜抑制。为此，研究小组将使用Live/Dead系统或生物通量类型的系统-通过可视化LasR GFP(生物信号)和POA1-LasB RFP(生物量)来完成。革兰氏阴性紫罗兰色杆菌将被用来证明通过缺乏紫色紫罗兰素的产生来抑制AHL信号。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月在葡萄牙举行的国际生物膜会议上发表，以及通过发表基于这项研究的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.