Synthetic Materials for Biofilm Inhibition

非技术性：该奖项由材料研究部生物材料计划授予爱荷华州立大学，旨在研究新型聚合物纳米颗粒，以抑制细菌群体感应(QS)。通过QS，细菌通过检测分泌到直接环境中的自动诱导物来识别彼此的存在。一旦达到自我诱导剂的阈值浓度，QS调节的基因就会被激活，以触发生物膜的形成，并增强病原菌的毒力。在生物膜中，细菌对抗生素和其他环境压力的抗药性可能会高出1000倍。80%的细菌感染与生物膜的形成有关，几乎所有的医疗器械都会受到生物膜的感染。克服细菌耐药性和生物被膜形成是世界各地科学家和工程师面临的紧迫和困难的挑战。这项拟议的研究旨在开发纳米催化剂，以模拟自然产生的自动诱导降解酶，选择性地破坏革兰氏阴性细菌的主要自动诱导。这项研究有可能影响到许多受细菌生物膜形成影响的领域，包括医疗保健、工程和农业。这项跨学科的研究将使学生研究人员接触到广泛的技能，并为他们通过尖端材料研究解决人类面临的大型问题做好准备。技术：尽管细菌具有单细胞性质，但它们可以相互交流，识别他人的存在。这个过程被称为群体感应(QS)，当信号分子(即自动诱导物)在细菌群落中分泌和积累时发生。自我诱导剂的阈值浓度会触发生物膜的形成，并增强病原菌的毒力。多重耐药细菌的出现和药物开发中新抗生素的短缺促使许多研究人员加紧寻找潜在的解决方案，特别是针对生物被膜状态的细菌。这项拟议的研究开发了聚合物纳米粒子催化剂，以选择性地结合和破坏革兰氏阴性细菌的主要自动诱导剂。将采取一些战略，在携带预期化学分解所需催化功能的水溶性纳米颗粒中创建催化口袋。降解自动诱导剂的动力学研究将与生物测试相结合，以确定最有效的生物膜抑制剂。通过拟议的研究，学生研究人员将接受广泛的技能培训，包括有机合成、生物学、抗菌研究、酶催化、物理有机化学、超分子化学和聚合物化学。此外，学生们将看到他们的工作与人类面临的重大问题之间的紧密联系，并体会到尖端科学研究的价值。因此，多学科的工作可以为来自化学或兽医背景的学生研究人员提供出色的培训。

Nontechnical: This award by the Biomaterials Program of the Division of Materials Research to Iowa State University is to study novel polymeric nanoparticles to suppress bacterial quorum sensing (QS). Through QS, bacteria recognize each others' presence by detecting auto-inducers secreted into the immediate environment. Once a threshold concentration is reached for the auto-inducers, QS-regulated genes are turned on to trigger biofilm formation and enhanced virulence for pathogenic bacteria. In biofilms, bacteria can be 1000-times more resistant to antibiotics and other environmental pressure. Eighty percent of all bacterial infections are related to biofilm formation and practically all medical devices are subject to biofilm infection. Overcoming bacterial resistance and biofilm formation is an urgent and difficult challenge to scientists and engineers worldwide. The proposed research aims to develop nanoparticle catalysts to mimic naturally occurring auto-inducer degrading enzymes to selectively destroy the main auto-inducer of gram negative bacteria. The research has the potential to impact numerous areas that are affected by bacterial biofilm formation including health care, engineering, and agriculture. This cross disciplinary research will expose student researchers to a wide range of skills and prepare them to solve large problems faced by humanity through cutting edge materials research.Technical: Despite their unicellular nature, bacteria can communicate with each other and recognize others' presence. The process, termed quorum sensing (QS), happens as signal molecules (i.e., auto-inducers) are secreted and accumulate within a bacterial community. A threshold concentration of the auto-inducer triggers biofilm formation and enhanced virulence for pathogenic bacteria. The emergence of multidrug resistant bacteria and shortage of new antibiotics in drug development prompted many researchers to search intensely for potential solutions, targeting bacteria in the biofilm state in particular. The proposed research develops polymeric nanoparticle catalysts to selectively bind and destroy the main auto-inducer of gram negative bacteria. A number of strategies will be pursued to create catalytic pockets in water soluble nanoparticles carrying the necessary catalytic functionalities for the intended chemical decomposition. Kinetic studies in the degradation of the auto-inducers will be combined with biological assays to identify the most potent biofilm inhibitors. With the proposed research, student researchers will be trained in a wide range of skills including organic synthesis, biology, antimicrobial research, enzyme catalysis, physical organic chemistry, supramolecular chemistry, and polymer chemistry. Moreover, the students will see a strong connection between their work and large problems faced by humans and appreciate the value of cutting edge scientific research. The multidisciplinary work thus can provide excellent training to the student researchers that come from either a chemistry or veterinary medicine background.