Examination of Staphylococcus aureus interactions with hemoglobin

描述（由申请人提供）：主要研究者（Boles博士）目前是爱荷华州大学的博士后研究员。 他在研究多种病原细菌的细菌生理学和生物膜发育方面具有丰富的经验。在接下来的12个月里，他计划在一家主要的研究机构获得终身教职，未来的研究重点是了解S。金黄色葡萄球菌生理学和发病机制。他的实验室的长期目标将是了解参与S。金黄色葡萄球菌从哺乳动物宿主蛋白质中获得铁，以及这些宿主蛋白质如何影响生物膜的形成和分散。本研究的重点是阐明S.金黄色葡萄球菌从血红蛋白中获得血红素（从而获得铁），并研究血红蛋白如何影响金黄色葡萄球菌。金黄色葡萄球菌基因表达和生物膜形成。初步研究发现，S。金黄色葡萄球菌胞外蛋白酶活性是从血红蛋白中获取铁所必需的，血红蛋白可以影响金黄色葡萄球菌的生产。金黄色葡萄球菌蛋白酶。本建议的具体目标是：1）识别特定的S。金黄色葡萄球菌细胞外蛋白酶从血红蛋白中获取血红素所必需的，2）确定血红蛋白对细胞外蛋白酶表达的调节作用，和3）检查血红蛋白对金黄色葡萄球菌的影响。金黄色葡萄球菌生物膜形成。博尔斯博士的研究计划与公共卫生有很大的相关性，因为S。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。 该项目的研究结果将增加对S.金黄色葡萄球菌的致病机制，并可能导致新的治疗选择治疗S。金黄色葡萄球菌感染

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.