Examination of Staphylococcus aureus interactions with hemoglobin

金黄色葡萄球菌与血红蛋白相互作用的检查

基本信息

批准号：
8019047
负责人：
BLAISE R BOLES
金额：
$ 10.8万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-01 至 2012-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The principal investigator, (Dr. Boles), is currently a postdoctoral fellow at the University of Iowa. He has significant experience studying bacterial physiology and biofilm development in multiple pathogenic bacterial species. Within the next 12 months, he plans on obtaining a tenure track academic position at a major research institute with a future research focus on understanding S. aureus physiology and pathogenesis. The long-term objectives of his laboratory will be to understand the molecular mechanisms involved in S. aureus iron acquisition from mammalian host proteins and how these host proteins influence biofilm formation and dispersal. The proposed research will focus on elucidating how S. aureus obtains heme (and therefore iron) from hemoglobin and examining how hemoglobin influences S. aureus gene expression and biofilm development. Preliminary work has uncovered that S. aureus extracellular protease activity is necessary for iron acquisition from hemoglobin and hemoglobin can influence the production of S. aureus proteases. The specific aims of this proposal are designed to 1) identify the specific S. aureus extracellular protease(s) necessary for heme acquisition from hemoglobin, 2) define the regulatory effects of hemoglobin on extracellular protease expression, and 3) examine the influence of hemoglobin on S. aureus biofilm formation. Dr. Boles' research plan has great relevance to public health as S. aureus is a major cause of infection and death in community and hospital associated infections. Findings from the proposed project will increase understanding of S. aureus pathogenic mechanisms and may lead to new therapeutic options for treating S. aureus infections.

描述（由申请人提供）：首席研究员（Boles 博士）目前是爱荷华大学的博士后研究员。他在研究多种病原菌的细菌生理学和生物膜发育方面拥有丰富的经验。在接下来的 12 个月内，他计划在一家大型研究机构获得终身教职学术职位，未来的研究重点是了解金黄色葡萄球菌的生理学和发病机制。他实验室的长期目标是了解金黄色葡萄球菌从哺乳动物宿主蛋白中获取铁所涉及的分子机制，以及这些宿主蛋白如何影响生物膜的形成和扩散。拟议的研究将重点阐明金黄色葡萄球菌如何从血红蛋白中获取血红素（以及铁），并研究血红蛋白如何影响金黄色葡萄球菌基因表达和生物膜发育。初步研究发现，金黄色葡萄球菌胞外蛋白酶活性对于从血红蛋白中获取铁是必需的，并且血红蛋白可以影响金黄色葡萄球菌蛋白酶的产生。该提案的具体目标是 1) 鉴定从血红蛋白获取血红素所需的特定金黄色葡萄球菌细胞外蛋白酶，2) 确定血红蛋白对细胞外蛋白酶表达的调节作用，以及 3) 检查血红蛋白的影响对金黄色葡萄球菌生物膜形成的影响。 Boles 博士的研究计划与公众健康密切相关，因为金黄色葡萄球菌是社区和医院相关感染中感染和死亡的主要原因。拟议项目的研究结果将增进对金黄色葡萄球菌致病机制的了解，并可能带来治疗金黄色葡萄球菌感染的新治疗选择。