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着能力可能在很大程度上是 归因于它产生的广泛的毒力因子，并与其利用的能力相结合 主机中的各种代谢壁ni。相反，它引起更多持续感染的能力 是其形成生物膜的倾向的函数，该过程通过植入而增强 医疗设备。当前的资金周期揭示了出色的发展过程 在生物膜形成期间发生的，包括多个发育阶段，随机基因 表达，以及不同结构的形成。基于这些初步结果，是 假设金黄色葡萄球菌生物膜发育的不同发育阶段是 在感染过程中最佳适应性所需。该假设将在三个特定的 目的包括1）定义从浮游生物到无柄生活方式的过渡涉及的步骤， 2）提供对双态开关的机械洞察力，3）证明了体内的作用 双重性。这些目标结合在一起，将为涉及的发展步骤提供重要的见解 在金黄色葡萄球菌生物膜形成中，并在体内定义了这些过程的相关性。常见 该项目的主题将是实验的高度协同性质 该计划的其他项目，尤其是探测毒力调节的实验 基因表达（项目3）和该法规的体内相关性（项目4）。一次 完成后，这些实验的结果将大大增强我们对金黄色葡萄球菌的理解 生物膜开发并洞悉这些复杂结构的特征 使它们如此顽固地进行临床干预。