Assessing the roles of biofilm structure and mechanics in pathogenic, persistent infections

在生物膜感染中发展了什么样的空间结构和机制，以及这种空间结构和机制是如何形成的。 机制影响生物膜感染的持久性和毒力，是未知的。长期目标是 找到诊断和治疗方法，解决结构和力学的多细胞，三- 在宿主体内的三维生物膜感染。本提案的目的是确定机制， 慢性伤口中条件致病菌铜绿假单胞菌的生物膜感染的结构，以及 这些物理特性如何影响疾病进程。核心假设是，空间结构和 力学是控制病毒毒力、抗生素抗性和免疫逃避的主要物理因素， 生物膜感染这项建议的基本理由是，完成这项工作将确定关键的物质目标， 预防、破坏或改善重要的生物膜形成病原体的生物膜感染。的 拟议的工作还将开发一个广泛适用的平台，用于评估生物膜的状态和影响 结构和机械学来研究其他感染生物。中心假设将通过追求三个测试 具体目标：1）确定体内生物膜感染的空间结构和机制; 2）确定如何 空间布局分化为不同的微环境; 3）确定空间结构的作用 和生物膜-中性粒细胞相互作用的机制。我们将通过创新的组合来实现这些目标。 生物和物理科学的分析和操纵技术。这些包括 最近开发的生物膜研究专用技术，以及已被 应用于生物膜材料的研究很少。这项研究意义重大，因为它将 确定哪些结构和机械特性应该是治疗目标。有着现实的指导意义 因为它将开发一个可以扩展到研究其他病原体（或细菌）的平台， 协同作用，为生物膜疗法开辟新的途径。这项工作将开发基础资源， 被其他研究人员用于铜绿假单胞菌和其他生物。对此的近期预期结果 工作的生物膜的结构和机械特性有助于临床影响的理解。 结果将立即产生重要的积极影响，因为它们将建立更好的理解 对生物膜的感染、毒力、耐药性和免疫系统的影响为重要病原体， 而且是长期的，因为它们为开发一套更好地处理生物膜的技术奠定了基础 感染.

What spatial structure and mechanics develops in biofilm infections, and how such spatial structure and mechanics impact the persistence and virulence of biofilm infections, is not known. The long-term goal is to find diagnostic and treatment approaches that address the structure and mechanics of multicellular, three- dimensional biofilm infections within the host. The objective of this proposal is to determine the mechanics and structure of biofilm infections of the opportunistic pathogen Pseudomonas aeruginosa in chronic wounds, and how these physical properties impact disease course. The central hypothesis is that spatial structure and mechanics are the major physical factors controlling virulence, antibiotic resistance, and immune evasion in biofilm infections. The rationale underlying this proposal is that completion will identify key physical targets for preventing, disrupting, or ameliorating biofilm infections for an important biofilm-forming pathogen. The proposed work will also develop a widely-applicable platform for assessing the state and impact of biofilm structure and mechanics for other infecting organisms. The central hypothesis will be tested by pursuing three specific aims: 1) Determine the spatial structure and mechanics of in vivo biofilm infections; 2) Determine how spatial arrangements differentiate into distinct microenvironments; 3) Determine the role of spatial structure and mechanics in biofilm-neutrophil interactions. We will pursue these aims using an innovative combination of analytical and manipulative techniques from both biological and physical sciences. These include both recently-developed techniques specific to biofilm studies, and more-established techniques that have been applied very little to the study of biofilm materials. The proposed research is significant, because it will determine which structural and mechanical characteristics should be therapeutic targets. It is also significant because it will develop a platform that can be extended to study other pathogens (or commensals) and synergies to open new avenues for biofilm therapies. This work will develop foundational resources that will be used by other researchers, for P. aeruginosa and other organisms. The proximate expected outcome of this work an understanding of which biofilm structural and mechanical characteristics contribute to clinical impact. The results will have an important positive impact immediately because they will establish better understanding of biofilm infection, virulence, and resistance to antibiotics and the immune system for an important pathogens, and long-term because they lay the groundwork to develop a suite of techniques for better treatment of biofilm infections.