Role of Staphylococcus aureus SpA in Microbial Competition and Host Colonization

描述（由申请人提供）：本提案详细介绍了Paul J Planet博士在传染病基础研究方面的五年综合计划。Planet博士设计了他的指导研究计划，以提供额外的科学培训和技能，使他能够成功地成为一名独立的研究者和医生科学家。Planet博士的科学培训目标是通过获得宿主-病原体免疫学、流行病学和微生物组研究领域的经验来增加他在分子微生物学和系统发育方面的背景。他的职业目标是成功地转变为一名独立调查员。Alice Prince医学博士将是Planet博士在科学和职业发展方面的主要导师。普林斯博士是宿主-病原体相互作用、先天免疫和传染病领域的领导者。Planet博士已经成立了一个咨询委员会，指导他的科学进步和职业发展，该委员会由微生物学家（Noah Fierer博士、Franklin Lowy博士、Barry Kreiswirth博士）组成，他们在微生物生态学、免疫学、流行病学、基因组学、动物模型和发病机制方面具有专业知识。他还将利用哥伦比亚大学的大量资源进行职业发展和科学合作。Planet博士的项目重点关注金黄色葡萄球菌在人体皮肤和粘膜组织上定植和持续存在的非凡能力。金黄色葡萄球菌的定植对疾病的传播至关重要，它是感染的主要危险因素。核心假设是金黄色葡萄球菌通过触发宿主的先天免疫反应来优先消除其他共生细菌竞争对手，从而提高其定植能力。在一个小鼠模型中，Planet博士最近发现金黄色葡萄球菌能够

DESCRIPTION (provided by applicant): This proposal details a comprehensive 5-year program for Dr. Paul J Planet's career development in basic research in Infectious Diseases. Dr. Planet has designed his mentored research program to provide both additional scientific training and skills that will allow him to succeed as an independent investigator and physician-scientist. Dr. Planet's scientific training objective is to add to his background in molecular microbiology and phylogenetics by gaining experience in the areas of host-pathogen immunology, epidemiology, and microbiome studies. His career objective is to successfully make the transition to being an independent investigator. Alice Prince M.D. will be Dr. Planet's primary mentor for scientific and career development. Dr. Prince is a leader in the fields of host-pathogen interactions, innate immunity, and infectious diseases. Dr. Planet has established an advisory committee that will guide his scientific progress and career development that is composed of microbiologists (Dr. Noah Fierer, Dr. Franklin Lowy, Dr. Barry Kreiswirth) with expertise in microbial ecology, immunology, epidemiology, genomics, animal models, and pathogenesis. He will also utilize the considerable resources for career development and scientific collaboration at Columbia University. Dr. Planet's project focuses on the remarkable ability of Staphylococcus aureus to colonize and persist on human skin and mucosal tissues. Colonization by S. aureus is critical for the spread of disease, and it is a major risk factor for infection. The central hypothesis is that Staphylococcus aureus improves its ability to colonize by triggering the host's innate immune response to preferentially eliminate other commensal bacterial competitors. In a mouse model, Dr. Planet recently found that the ability of S. aureus to manipulate the host's immune response is due, in part, to production of Protein A (SpA). He has also shown that the variable tandem repeat region (Xr) of SpA appears to be critical for this effect. Preliminary data suggests that SpA may act by increasing expression of antimicrobial peptides produced by the host epithelium. The specific aims of the proposal are to: (1) Test the hypothesis that the Xr region of SpA affects colonization of resident flora in a mouse model, and delineate the specific ecological shifts that occur. (2) Determine the primary elements of the human innate immune response that are triggered by Xr leading to clearance of other flora.