Staphylococcus aureus biofilms: in vitro and in vivo studies

金黄色葡萄球菌生物膜：体外和体内研究

• 批准号: 7320471
• 负责人: Mark E Shirtliff
• 金额: $ 37.13万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7320471
• 关键词: Animal Model; Antibodies; Antigens; Bacillus (bacterium); Cessation of life; Chronic; Clostridium; Communities; Data; Development; Disinfection; Evaluation; Excision; Gene Expression; Gene Expression Profile; Genus staphylococcus; Glycocalyx; Goals; Growth; Hospitalization; Human; Immune system; Immunity; Immunization; Implant; In Vitro; Infection; Infection prevention; Inflammatory Response; Interleukin-12; Joints; Laboratories; Listeria; Mass Spectrum Analysis; Mediating; Medical Device; Microbe; Microbial Biofilms; Modeling; Molecular; Morbidity - disease rate; Nature; Numbers; Oryctolagus cuniculus; Patients; Phagocytes; Phase; Physiological; Production; Proteins; Proteome; Proteomics; Research; Research Personnel; Resolution; Standards of Weights and Measures; Staphylococcus aureus; Streptococcus; Superantigens; Surface; System; Time; Toxin; Two-Dimensional Gel Electrophoresis; United States; Virulence Factors; antimicrobial drug; capsule; cell mediated immune response; cytokine; implantation; in vivo; microbial; mortality; novel; prevent; programs; quorum sensing; response; retinal rods; two-dimensional; vaccine development

DESCRIPTION (provided by applicant): Staphylococcus aureus is a gram positive, ubiquitous bacterial species, with the predominant reservoir in nature being humans. The increased use of implanted medical devices such as intramedullary rods, screws, plates, and artificial joints has provided a physiological niche for microbes to cause infections. While a number of bacterial species may cause microbial fouling of indwelling medical devices, S. aureus causes a majority of these infections, producing high chronicity, morbidity, and mortality. One of the important mechanisms by which S. aureus is able to cause persistent infections on indwelling medical devices is through colonizing and synthesizing a "slime" layer, termed the glycocalyx or biofilm. This layer prevents infection resolution by antimicrobial agents and host phagocytic cells. Once an implant is colonized and chronic infection ensues, the standard treatment option is implant removal. This proposal seeks to identify S. aureus gene products with upregulated production in biofilms using two dimensional (2D) gel electrophoresis. Selected up-regulated proteins will then be evaluated, first, for their ability to be recognized by the host immune system during an in vivo biofilm infection, and second, for their protective efficacy in preventing infections in an implant-associated infection model in rabbits. The data generated here may contribute to the eventual development of a vaccine against S. aureus biofilms infections in humans. In addition, this proposal will also contribute to a more complete understanding of the bacterial factors involved in S. aureus biofilm formation and maturation. This understanding will enable one to create novel materials, surfaces, and/or disinfection strategies that resist or eliminate staphylococcal fouling and biofilm formation. Also, the proteome will be compared to transcriptome DMA microarray studies already completed in the Pi's laboratory in order to determine the global interrelation between gene expression and protein production for S. aureus biofilms grown under flow, thereby allowing staphylococci to be understood at a new level. Lastly, the results obtained in the evaluation of S. aureus biofilm formation may be used as a model for the biofilm formation by other closely related gram positive bacterial species, including Streptococcus spp., Listeria spp., Clostridium spp. and Bacillus spp.

描述（由申请方提供）：金黄色葡萄球菌是一种革兰氏阳性、普遍存在的细菌菌种，自然界中的主要宿主是人类。越来越多地使用植入式医疗器械，如髓内杆、螺钉、板和人工关节，为微生物提供了引起感染的生理生态位。虽然许多细菌物种可能会导致留置医疗器械的微生物污染，但S。金黄色葡萄球菌引起大多数这些感染，产生高慢性、发病率和死亡率。S.金黄色葡萄球菌能够通过定殖和合成称为糖萼或生物膜的“粘液”层而在留置医疗装置上引起持续感染。该层防止抗微生物剂和宿主吞噬细胞的感染消退。一旦种植体定植并形成慢性感染，标准治疗选择是取出种植体。该建议旨在确定S。使用二维（2D）凝胶电泳检测在生物膜中具有上调产量的金黄色葡萄球菌基因产物。然后将首先评估所选择的上调蛋白在体内生物膜感染期间被宿主免疫系统识别的能力，其次评估其在兔的植入物相关感染模型中预防感染的保护功效。这里产生的数据可能有助于最终开发针对S.金黄色葡萄球菌生物膜感染人类。此外，这一建议也将有助于更全面地了解参与S.金黄色葡萄球菌生物膜形成和成熟。这种理解将使人们能够创造新的材料，表面和/或消毒策略，抵抗或消除葡萄球菌污垢和生物膜形成。此外，蛋白质组将与Pi实验室已经完成的转录组DMA微阵列研究进行比较，以确定S.金黄色葡萄球菌生物膜在流动下生长，从而使葡萄球菌被理解在一个新的水平。最后，对S.金黄色葡萄球菌生物膜形成可用作其它密切相关的革兰氏阳性细菌物种，包括链球菌属，李斯特菌属，梭菌属和芽孢杆菌属（Bacillus spp.）