Urethral Catheter-Associated Polybacterial Biofilm Formation and Dispersal

导尿管相关多细菌生物膜的形成和扩散

• 批准号: 8812891
• 负责人: REMBERT PIEPER
• 金额: $ 31.05万
• 依托单位: J. CRAIG VENTER INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-15 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8812891
• 关键词: Adverse effects; Affect; Allergic Disease; Antibiotic Therapy; Bacteria; Bacteriuria; Biochemical; Bioinformatics; Biological; Biological Models; Catheters; Clinic; Clinical; Communicable Diseases; Communication; Competitive Behavior; Complex; Computer software; Contracts; Culture Media; Data; Data Set; Databases; Development; Diagnosis; Disease; Environment; Equilibrium; Exhibits; Genomics; Growth; Health; Hospitals; Host Defense; Human; Immune response; In Vitro; Incidence; Individual; Indwelling Catheter; Infection; Infectious Agent; Inflammatory; Inflammatory Response; Lead; Left; Liquid substance; Longitudinal Studies; Metagenomics; Methods; Microbe; Microbial Biofilms; Modeling; Molecular; Molecular Analysis; Movement; Organism; Patients; Pattern; Production; Proteomics; Quality Control; Relative (related person); Reproducibility; Research Design; Ribosomal RNA; Sampling; Shotguns; Signal Transduction; Solutions; Specimen; Staging; Surface; Surveys; System; Systems Biology; Technology; Time; Urethra; Urinary tract; Urinary tract infection; Urine; Work; antimicrobial; base; biosignature; catheter associated UTI; gut microbiota; in vitro Model; in vivo; ionization; metabolomics; metagenome; metagenomic sequencing; microbial; microbial community; pathogen; protein metabolite; rRNA Genes; research study; response; statistics; urinary

Biofilms are matrix-enclosed microbial assemblies adhering to non-biological and biological surfaces. They undergo dynamic environment-dependent changes. Many biofilms constitute complex microbial communities rather than assemblies composed of one or a few species. Species uncultivable under most in vitro growth conditions may contribute to these biofilms. The most frequently occurring biofilm-associated infection world- wide is the urinary tract infection (UTI). Nosocomial indwelling catheter-associated urinary tract infections (CA- UTI) are contracted by more than 1 million patients per year in the U.S. alone. Bacteria colonizing the catheters are highly adapted to the production of biofilms. Reasons as to why bacterial colonization of long term-inserted urethral catheters results in CA-UTI versus asymptomatic bacteriuria (CA-ASB) are essentially not known, and causative factors pertaining to the host environment and complexity of microbial biofilms may be implicated. Recent 16S rRNA gene surveys have indicated that microbial complexity of CA biofilms and urinary precipitates is higher than previously thought. The overall objective of this proposal is to characterize the dynamic formation and dispersal of these biofilms, as well as the triggers controlling relative human host inertia versus inflammatory responses. We hypothesize thata dynamic balance is established among pathogenic and lesser-characterized generally harmless bacteria, influencing the extent of the human host's immune response. A systems biology approach allows integration of diverse molecular datasets to elucidate signaling among microbial species responsible for cooperative as well as competitive behaviors and with the urothelial host defense system. The first Specific Aim is to profile the metagenome, metaproteome and metabolome of CA biofilms and dispersed bacterial aggregates from clinical cases in a longitudinal study design. The second Specific Aim is to develop and evaluate in vitro model systems inoculated with CA biofilm isolates and perform 'omics analysis on in vitro developing biofilms. The in vitro model systems will be based on cultivation of CA biofilm isolates with controlled level of oxygenation and synthetic urine as growth media. The third Specific Aim is to integrate and analyze metagenomic, metaproteomic and metabolomic datasets using advanced bioinformatics and multivariate statistics methods. We intend to identify biosignatures at five different levels: species, bacterial and host proteins and metabolites that characterize patterns of microbial communication with each other in the time domain and allow assessments of host tolerance towards and host defense against polybacterial colonization. We predict that the results will not only have profound implications as regards biofilm dynamics, but will also reveal biosignatures relevant in the context of diseases not limited to one infectious agent other than CA-UTI. 2.

生物膜是粘附在非生物和生物表面的基质封闭的微生物组件。他们 经历动态环境依赖性变化。许多生物膜构成复杂的微生物群落 而不是由一个或几种物种组成的组件。在大多数体外生长下无法养殖的物种 条件可能会导致这些生物膜。最常见的生物膜相关感染世界 - 尿路感染（UTI）宽。医院的留置导管相关的尿路感染（CA- - 仅在美国，UTI）每年就有超过100万名患者签约。细菌定居导管 高度适应生物膜的生产。关于为什么长期插入细菌定植的原因 尿道导管会导致CA-UTI与无症状细菌（Ca-ASB）的尿道导管基本上尚不清楚，并且 可能涉及与宿主环境和微生物生物膜复杂性有关的病因。 最近的16S rRNA基因调查表明，CA生物膜和尿液的微生物复杂性 沉淀物高于以前想象的。该提议的总体目的是表征 这些生物膜的动态形成和分散以及控制相对人类宿主惯性的触发器 与炎症反应相对于炎症。我们假设在致病性和 较少的特征通常无害的细菌影响了人类宿主的免疫反应程度。 系统生物学方法允许将各种分子数据集集成以阐明信号传导 负责合作和竞争行为的微生物物种以及尿路上皮宿主 国防系统。第一个具体目的是介绍CA的元基因组，元蛋白质组和代谢组 纵向研究设计中的临床病例中的生物膜和分散细菌骨料。第二个 具体目的是开发和评估与CA生物膜分离株接种的体外模型系统和 对体外发育生物膜进行OMICS分析。体外模型系统将基于种植 具有控制水平的氧合水平和合成尿液作为生长培养基的Ca生物膜分离株的。第三 具体目的是使用使用元基因组，元蛋白质组学和代谢组数据集进行整合和分析 高级生物信息学和多元统计方法。我们打算在五个不同的地方识别生物签名 水平：物种，细菌和宿主蛋白质和代谢物，这些蛋白质和代谢产物表征了微生物的模式 在时间域中彼此交流，并允许对宿主对和主机的容忍度进行评估 防御多分裂定植。我们预测结果不仅会产生深远的影响 关于生物膜动态，但也将揭示在不限于疾病的背景下相关的生物签名 Ca-uti以外的一种传染剂。 2。