Characterization of a novel S. aureus biofilm polysaccharide

新型金黄色葡萄球菌生物膜多糖的表征

基本信息

批准号：
10373045
负责人：
Chia Y. Lee
金额：
$ 22.8万
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：
2021
资助国家：
美国
起止时间：
2021-03-16 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10373045
关键词：
Antibiotic Resistance Antibiotic Therapy Antibodies Applications Grants Bacteria Bacterial Antibiotic Resistance Biochemical Carbohydrates Cause of Death Cells Chemicals Chromatography Chromosomes Communities Confocal Microscopy DNA Development Diagnostic Disease Extracellular Matrix Failure Foundations Gel Gene Cluster Genes Genome Genus staphylococcus Goals HIV Hospitals Immune Immune system Implant In Vitro Infection Knowledge Mass Spectrum Analysis Methods Microbial Biofilms Modeling Molecular Mus Mutation NMR Spectroscopy Names Operon Organism Osteomyelitis Pattern Polyacrylamide Gel Electrophoresis Polysaccharides Production Proteins Reporting Role Solid Staphylococcal Infections Staphylococcus aureus Structure Surface System Tissues Variant Virulence Virulence Factors Virulent bacterial community bacterial resistance chronic infection emerging antibiotic resistance experimental study extracellular gene synthesis genetic approach genetic resistance genomic locus human disease human pathogen implantable device in vivo mutant new therapeutic target novel novel diagnostics pathogen pathogenic bacteria protein complex resistance gene resistant strain targeted treatment trait

项目摘要

Summary Staphylocuccus aureus is a significant human pathogen that causes a wide range of diseases, some of which are serious and difficult to treat. Current treatment methods are largely limited to antibiotic therapy. However, S. aureus is capable of forming biofilm on implants or tissues rendering the bacteria resistance to antibiotics and to host immune defense system without acqiuring genetic resistance traits. Thus, biofilm formation often leads to treament failures. Biofilms are bacterial communities consist of multiple layers of bacterial cells encased within an extracellular matrix that keeps the bacteria within the biofilm structure. To date, staphylococcal biofilm matrix has been shown to consist of polysaccharides, proteins and extracellular DNA but the composition is not been fully defined. Understanding biofilm matrix composition is therefore critical to unveil biofilm formaiton mechanism and provide potential targets for therapeutic or diagnostic development. Diverse biofilm matrix proteins have been reported but only very few species of matrix polysaccharide have been identified. We have shown that mutations in an previously uncharacterized gene cluster of putative polysaccharide sythesis genes in the S. aureus genome reduced biofilm formation. These results indicate that the gene cluster is involved in the production of a novel polysaccharide, which contributes to S. aureus virulence by promoting biofilm formation. Thus, the goal of this application is to verify and study this novel polysaccharide. To this end, we will molecularly characterize the gene cluster and biochemically identify the novel polysaccharide in Aim 1 and study the role of this polysacharide in biofilm formation and in virulence in an implant bone infection model in Aim 2.

概括金黄色葡萄球菌是一种重要的人类病原体，可引起各种疾病，其中一些疾病严重且难以治疗。当前的治疗方法在很大程度上仅限于抗生素治疗。但是，S。金黄色葡萄球菌能够在植入物或组织上形成生物膜，从而使细菌耐药性抗生素和抗生素耐药性宿主免疫防御系统，没有遗传抗性特征。因此，生物膜的形成通常会导致不良的失败。生物膜是细菌群落，由包含在内的多层细菌细胞组成细胞外基质将细菌保持在生物膜结构中。迄今为止，葡萄球菌生物膜基质已显示由多糖，蛋白质和细胞外DNA组成，但并非成分完全定义。因此，了解生物膜基质组合物对于揭示生物膜征膜机制至关重要并为治疗或诊断发展提供潜在的目标。多种生物膜基质蛋白具有报道了，但仅发现了很少的基质多糖。我们已经表明在S. 金黄色基因组降低了生物膜的形成。这些结果表明该基因簇参与产生一种新型的多糖，该多糖通过促进生物膜形成有助于金黄色葡萄球菌的毒力。因此，该应用的目的是验证和研究这种新型多糖。为此，我们将分子表征基因簇，并在生化中识别AIM 1中的新型多糖并研究在AIM 2中，这种生物膜形成和毒力中的多恰鱼在植入骨感染模型中的毒力。