Proteomic analysis of S aureus biofilm in vivo

体内金黄色葡萄球菌生物膜的蛋白质组学分析

• 批准号: 8707068
• 负责人: Chia Y. Lee
• 金额: $ 18.63万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-07 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8707068
• 关键词: Accounting; Animal Model; Animals; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antibodies; Applications Grants; Bacteria; Bacterial Proteins; Catheters; Cause of Death; Cells; Chronic; Clinical; DNA; Development; Disease; Environment; Extracellular Matrix; Foundations; General Population; Genes; Goals; HIV; Harvest; Hospitals; Host Defense; Human; Immune system; Implant; In Vitro; Incidence; Individual; Infection; Knowledge; Lead; Methods; Microbial Biofilms; Modeling; Nature; Orthopedics; Polysaccharides; Production; Protein S; Proteins; Proteomics; Rattus; Resistance; Sampling; Site; Solid; Staphylococcal Infections; Staphylococcus aureus; Surface; Therapeutic; Translating; Treatment Failure; Validation; Variant; Virulence; Virulence Factors; Virulent; assault; bacterial resistance; base; clinically relevant; combat; extracellular; implantable device; in vivo; novel; novel diagnostics; pathogen; prevent; public health relevance; research study; resistant strain; therapeutic target

DESCRIPTION (provided by applicant): Staphylocuccus aureus is a major human pathogen that causes a range of diseases. The incidence of staphylococcal infections continues to rise. Current methods of treatment rely almost exclusively on antibiotic therapy. Biofilm formation is a major contributor of S. aureus virulence because it protects the bacteria from antibiotics or host immune system. Specifically, biofilms provide intrinsic resistance to antibiotics and protection from host defenses, which leads to treatment failures. Biofilms consist of multiple layers of bacterial cells contained within an extracellular matrix that keeps the biofilm intact. Understanding the nature of biofilm matrix could lead to new methods to prevent biofilm formation or eradicate bacteria within a biofilm, thus providing a way to overcome the therapeutic recalcitrance of biofilm-associated infections. Factors previously shown to contribute to biofilm formation in S. aureus include surface-associated proteins, exopolysaccarides, and, extracellular DNA, but to date the contribution of these components to staphylococcal biofilm-associated infections has not been defined. More importantly, we do not fully understand the composition of biofilm matrix, especially the protein components, in biofilms formed during an infection. The goal of this application is to identify proteins in biofilms from an infection site sing a suitable animal model. To this end, we have recently developed a rat model of implant-associated orthopedics infection allowing us to isolate sufficient bacteria from an infection site o identify bacterial components directly using an advanced proteomic method. Thus, in this application, we propose to comprehensively identify proteins in biofilm matrix produced under in vivo conditions (Aim 1) and to validate the presence of a set of prioritized individual components in the infection site (Aim 2).

描述（由申请人提供）：金黄色葡萄球菌是一种主要的人类病原体，可引起一系列疾病。葡萄球菌感染的发病率持续上升。目前的治疗方法几乎完全依赖抗生素治疗。生物膜的形成是金黄色葡萄球菌毒力的主要贡献者，因为它可以保护细菌免受抗生素或宿主免疫系统的侵害。具体来说，生物膜提供了对抗生素的内在抵抗力和免受宿主防御的保护，这会导致治疗失败。生物膜由多层细菌细胞组成，细胞外基质内含有保持生物膜完整的细胞外基质。了解生物膜基质的性质可能会带来防止生物膜形成或根除生物膜内细菌的新方法，从而提供一种克服生物膜相关感染的治疗难点的方法。先前显示有助于金黄色葡萄球菌生物膜形成的因素包括表面相关蛋白、胞外多糖和细胞外DNA，但迄今为止这些成分对葡萄球菌生物膜相关感染的贡献尚未确定。更重要的是，我们还不完全了解感染过程中形成的生物膜中生物膜基质的组成，特别是蛋白质成分。该应用的目标是通过合适的动物模型识别感染部位生物膜中的蛋白质。为此，我们最近开发了一种植入物相关骨科感染的大鼠模型，使我们能够从感染部位分离出足够的细菌，或使用先进的蛋白质组学方法直接鉴定细菌成分。因此，在本应用中，我们建议全面鉴定体内条件下产生的生物膜基质中的蛋白质（目标 1），并验证感染部位是否存在一组优先的单个成分（目标 2）。