Staphylococcal biofilm and disease

描述(申请人提供)：金黄色葡萄球菌历来是全球人类医院感染的主要原因。在过去的几十年里，携带多种抗生素耐药决定因素的耐甲氧西林金黄色葡萄球菌(MRSA)的出现，使得可用的治疗选择相对较少。今天，这些毒株已经进入社区，现在构成了非常严重的公共卫生威胁，每年造成的死亡人数超过艾滋病毒/艾滋病。内布拉斯加大学医学中心致力于通过聘请几名新的研究人员，并与地区调查人员的协调合作，推进对葡萄球菌的研究，这些调查人员都专注于这种重要的病原体。这些研究人员在葡萄球菌的各个方面都有专业知识，包括：葡萄球菌感染的生物膜发育、基因调控、生理学和免疫学。该研究小组将在这一应用中检验的假设是，金黄色葡萄球菌生物膜的形成涉及影响宿主免疫反应的复杂发育过程。该应用包括围绕葡萄球菌生物膜和疾病的四个项目，包括：生物膜发育过程中调节细胞死亡(项目1，K.Bayles)；精氨酸代谢对葡萄球菌生物膜形成的影响(项目2，P.Fey)；核酸酶在生物膜发育和疾病中的作用(项目3，A.Horswill)；以及对金黄色葡萄球菌生物膜的先天免疫(项目4，T.Kielian)。这些核心包括：生物膜生长和分析核心(核心A，J.Bose)；生物成像核心(核心B，T.Fritz)；以及管理核心(核心C，K.Bayles)。每个项目都涉及高度协作和协同的研究努力，并严重依赖核心。这些努力将对我们理解葡萄球菌中生物膜的形成及其对宿主反应的影响产生重大影响。最终，这些研究将为治疗葡萄球菌感染的新的治疗方法铺平道路。

DESCRIPTION (provided by applicant): Staphylococcus aureus has historically been a leading cause of nosocomial infections in humans worldwide. In the past several decades the emergence of methicillin-resistant S. aureus (MRSA) harboring multiple antibiotic resistance determinants has left relatively few therapeutic options available. Today, these strains have made their way into the community and now pose a very serious public health threat, causing more deaths per year than HIV-AIDS. The University of Nebraska Medical Center has committed to advancing research into the staphylococci with the hiring of several new researchers, and the concerted collaboration with regional investigators, who are all focused on this important pathogen. These researchers have expertise in varied aspects of the staphylococci including: biofilm development, gene regulation, physiology, and the immunology of staphylococcal infections. The hypothesis to be tested by this team in this application is that S. aureus biofilm formation involves complex developmental processes that affect the host immune response. The application includes four projects centered around staphylococcal biofilm and disease including: regulated cell death during biofilm development (Project 1, K. Bayles); effect of arginine metabolism on biofilm formation in the staphylococci (Project 2, P. Fey); the role of nuclease in biofilm development and disease (Project 3, A. Horswill); and innate immunity to S. aureus biofilm (Project 4, T. Kielian). The cores include: Biofilm Growth and Analysis Core (Core A, J. Bose); Bioimaging Core (Core B, T. Fritz); and Administrative Core (Core C, K. Bayles). Each project involves highly collaborative and synergistic research endeavors and relies heavily on the cores. These efforts will have a dramatic impact on our understanding of biofilm formation in the staphylococci and the effect it has on the host response. Ultimately, these studies will pave the way for novel therapeutic approaches for the treatment of staphylococcal infections.