Synthetic Materials for Biofilm Inhibition

用于生物膜抑制的合成材料

• 批准号: 1464927
• 负责人: Yan Zhao
• 金额: $ 57万
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1464927&HistoricalAwards=false
• 关键词: Synthetic; Materials; Biofilm; Inhibition

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.

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诱导物来识别彼此的存在。一旦达到自诱导物的阈值浓度，QS调节的基因被打开以触发生物膜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抵抗力可以提高1000倍。80%的细菌感染与生物膜形成有关，几乎所有医疗器械都会受到生物膜感染。克服细菌耐药性和生物膜形成是全世界科学家和工程师面临的紧迫而艰巨的挑战。该研究旨在开发纳米颗粒催化剂，以模拟天然存在的自诱导物降解酶，从而选择性地破坏革兰氏阴性菌的主要自诱导物。这项研究有可能影响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掌握广泛的技能，并为他们通过尖端材料研究解决人类面临的重大问题做好准备。技术：尽管细菌具有单细胞性质，但它们可以相互交流并识别其他细菌的存在。该过程被称为群体感应（QS），作为信号分子（即，自身诱导物）被分泌并在细菌群落内积累。自诱导物的阈值浓度触发生物膜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积极寻找潜在的解决方案，特别是针对生物膜状态的细菌。拟议的研究开发了聚合物纳米颗粒催化剂，以选择性地结合和破坏革兰氏阴性菌的主要自诱导物。将采用许多策略来在水溶性纳米颗粒中产生催化口袋，所述催化口袋携带用于预期化学分解的必要催化功能。自诱导物降解的动力学研究将与生物测定相结合，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和人类面临的大问题之间的紧密联系，并欣赏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良好的培训。