The S. aureus biofilm lifecycle

金黄色葡萄球菌生物膜生命周期

• 批准号: 10461794
• 负责人: KENNETH W. BAYLES
• 金额: $ 40.43万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10461794
• 关键词: Antibiotics; Bioinformatics; Cell Differentiation process; Characteristics; Clinical; Complex; Development; Developmental Process; Disease; Funding; Gene Expression; Genetic Transcription; Genus staphylococcus; Goals; Immune system; Infection; Intervention; Life Style; Medical Device; Metabolic; Microbial Biofilms; Molecular; Mus; Nature; Population; Process; Program Research Project Grants; Regulation; Research; Role; Staphylococcus aureus; Structure; Testing; Virulence; Virulence Factors; Visualization; Zebrafish; acute infection; base; chronic infection; design; experimental study; fitness; implantation; in vivo; insight; mutant; programs

The remarkable ability of Staphylococcus aureus to cause acute infections can be largely attributed to the wide array of virulence factors it produces, combined with its ability to exploit various metabolic niches within a host. In contrast, its ability to cause more persistent infections is a function of its propensity to form biofilm, a process that is enhanced by the implantation of medical devices. The current funding cycle has revealed remarkable developmental processes that occur during biofilm formation, including multiple developmental stages, stochastic gene expression, and the formation of distinct structures. Based on these preliminary results, it is hypothesized that the distinct developmental stages of S. aureus biofilm development are required for optimal fitness during infection. This hypothesis will be tested in three specific aims including to 1) define the steps involved in the transition from a planktonic to sessile lifestyle, 2) provide mechanistic insight into the bistable switch, and 3) demonstrate the in vivo role of bistability. Combined, these aims will provide critical insight into the developmental steps involved in S. aureus biofilm formation and define the relevance of these processes in vivo. A common theme of this project will be the highly synergistic nature of the experiments in the context of the other projects of this program, particularly the experiments probing the regulation of virulence gene expression (Project 3) and the in vivo relevance of this regulation (Project 4). Once completed, the results of these experiments will greatly enhance our understanding of S. aureus biofilm development and provide insight into the characteristics of these complex structures that make them so recalcitrant to clinical intervention.

金黄色葡萄球菌引起急性感染的显著能力在很大程度上可以是 这归因于它产生的各种毒力因子，以及它利用 宿主体内的各种代谢生态位与此相反，它能够引起更持久的感染， 是其形成生物膜的倾向的函数，该过程通过植入 医疗器械目前的供资周期显示出显著的发展进程 包括多个发育阶段，随机基因， 表达，以及不同结构的形成。根据这些初步结果， 假设S.金黄色葡萄球菌生物膜的形成是 在感染期间保持最佳状态所需的。这一假设将在三个具体的 目标包括1）定义从浮游生活方式到固着生活方式转变所涉及的步骤， 2)提供了对β-淀粉样蛋白开关的机制性认识，以及3）证明了β-淀粉样蛋白在体内的作用。 双稳态结合起来，这些目标将为所涉及的发展步骤提供重要的见解 in S.金黄色葡萄球菌生物膜的形成，并确定这些过程在体内的相关性。一个共同 本项目的主题将是实验的高度协同性， 该计划的其他项目，特别是探索毒力调节的实验 基因表达（项目3）和这种调节的体内相关性（项目4）。一旦 这些实验的结果将大大加深我们对S.金黄色 生物膜的发展，并提供深入了解这些复杂结构的特点， 使他们如此抗拒临床干预。