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

基本信息

批准号：
8833246
负责人：
Chia Y. Lee
金额：
$ 22.35万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-07 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8833246
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 Goals HIV Harvest Health 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 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 research study resistance gene resistant strain therapeutic target

项目摘要

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）：金黄色葡萄球菌是引起各种疾病的主要人类病原体。葡萄球菌感染的发生率继续升高。当前的治疗方法几乎完全依赖于抗生素治疗。生物膜形成是金黄色葡萄球菌毒力的主要因素，因为它可以保护细菌免受抗生素或宿主免疫系统的影响。具体而言，生物膜为抗生素提供了固有的抵抗力，并防止了宿主防御能力，从而导致治疗失败。生物膜由包含在细胞外基质中的多层细菌细胞组成，以使生物膜完好无损。了解生物膜基质的性质可能会导致新的方法防止生物膜形成或消除生物膜内的细菌，从而提供一种方法来克服生物膜相关感染的治疗性重新ciTCITRANE。先前显示的因金黄色葡萄球菌形成的因素包括表面相关的蛋白质，外po省和细胞外DNA，但迄今为止尚未定义这些成分对葡萄球菌生物膜相关感染的贡献。更重要的是，我们不完全了解在感染过程中形成的生物膜中生物膜基质（尤其是蛋白质成分）的组成。该应用的目的是从感染部位鉴定生物膜中的蛋白质唱出合适的动物模型。为此，我们最近开发了一种与植入物相关的骨科感染的大鼠模型，使我们能够使用先进的蛋白质组学方法直接鉴定细菌成分，从而使我们能够从感染部位隔离足够的细菌。因此，在此应用中，我们建议在体内条件下（AIM 1）中全面鉴定生物膜基质中的蛋白质，并验证感染部位中一组优先的单个成分的存在（AIM 2）。