ENG-EPSRC EFRI ELiS: Developing probiotic interventions to reduce the emergence and persistence of pathogens in built environments

建筑环境(BE)的感染风险是不可避免的。居民的肺部、鼻窦和皮肤上都携带有感染性物质。他们还可以通过接触受污染的表面而感染病原体。干燥、营养不良的医疗环境是理解毒力和耐药性如何在表面出现和持续的模型系统。与传统的清洁产品相比，含有芽孢杆菌孢子的清洁产品可以将硬质表面上的多药耐药菌(MDRO)的丰度降低50-89%。初步数据表明，芽孢杆菌可以竞争性地排除表面上的MDRO。这需要不断地重复使用活性芽孢杆菌，这在许多情况下是不可行的。因此，有人建议设计新的芽孢杆菌菌种，以促进长期生存并减少MDRO的丰度。这些材料将被整合到新的表面材料中。最后，将对建筑参与者进行道德监督研究。该团队将试图了解如何使用具有芽孢杆菌活性的材料，提高对这些创新的公民责任，并确定它们的使用参数。该项目还将促进对代表性不足的少数群体的公平招聘和跨学科培训机会，以及向国家利益攸关方传播成果的广泛方法。这项提议的目标是设计出能够生存和排除病原体的芽孢杆菌菌株，并将它们部署到多孔建筑材料上。PI和Co-PI将设计出芽孢杆菌菌株，当整合到多孔建筑材料中时，这些菌株表现出存活和病原体排斥特性。疗效将通过竞争性排除MDRO和长期生存能力来量化。(I)对不同表面材料上的芽孢杆菌-病原菌竞争进行生化模拟，(Ii)对枯草杆菌菌株进行遗传操作以提高活性和持久性，以及(Iii)将菌株整合到复合材料中，这一迭代过程将有助于开发最佳的菌株结构。为了量化材料部署对人类和环境健康的影响，将对建筑居民进行调查，以了解人们对这些创新的公民责任的看法以及采用这些创新的社会障碍。拟议的工作将产生广泛的影响。该小组将促进公平招聘和指导工程学专业任职人数不足的受训人员。研究生行业实习将通过诺维信和高乐氏的两次实习提供，诺维信和高乐氏积极从事益生菌清洁产品的开发。一个独立的研究小组将对计划要素进行形成性和终结性评估。最后，与ASHRAE的合作将促进这些调查的结果在行业内广泛传播。这一奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The risk of infection in built environments (BE) is unavoidable. Inhabitants carry infection agents in their lungs and sinuses, and on their skin. They can also acquire infectious agents through contact with contaminated surfaces. Dry, nutrient poor healthcare environments are model systems to understand how virulence and drug resistance emerges and persists on surfaces. Bacillus spore containing cleaning products have been shown to reduce Multi-Drug Resistant Organism (MDRO) abundance on hard surfaces by 50-89% when compared to traditional cleaning products. Preliminary data suggests that Bacillus can competitively exclude MDROs on surfaces. This requires continual reapplication of active Bacillus, which is not feasible in many settings. Therefore, it is proposed to engineer new Bacillus species that promote long-term viability and reduce abundance of MDROs. These will be integrated into new surface materials. Finally, ethical oversight studies with building participants will be performed. The team will attempt to understand how deployment of Bacillus-active materials can be used improve civic responsibility for these innovations as well as define the parameters for their use. This project will also promote equitable recruitment and transdisciplinary training opportunities for underrepresented minorities and broad approaches to disseminate results to national stakeholders.The goal of this proposal is to engineer Bacillus strains for survival and pathogen exclusion and deploy them onto or into porous building materials. The PI and Co-PIs will engineer Bacillus strains that exhibit survival and pathogen exclusion traits when integrated into porous building materials. Efficacy will be quantified by competitive exclusion of MDROs and long-term viability. Deploying an iterative process of (i) biochemical modeling of Bacillus-pathogen competition on different surface materials, (ii) genetic manipulation of the B. subtilis strains to improve activity and persistence, and (iii) integration of strains into composite materials will help to develop optimal strain constructions. To quantify perceived human and environmental health impacts from material deployment, building inhabitants will be surveyed to understand perceptions of civic responsibility for these innovations and social barriers to adoption. The proposed work will have broad impact. The team will promote the equitable recruitment and mentorship of trainees underrepresented in Engineering. Graduate industry internships will be provided in molecular engineering through two internships with Novozymes and Clorox who are actively pursuing probiotic cleaning product development. An independent research group will perform formative and summative assessment of the program elements. Finally, collaboration with ASHRAE will facilitate dissemination of the results of these investigations broadly within the industry.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.