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

• 批准号: 7638720
• 负责人: BLAISE R BOLES
• 金额: $ 15.96万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7638720
• 关键词: Address; Affect; Antigens; Antimicrobial Resistance; Bacteria; Bacterial Physiology; Cell Communication; Cells; Cessation of life; Characteristics; Community Hospitals; Data; Development; Exhibits; Extracellular Matrix; Future; Gene Expression; Growth; Heme; Hemoglobin; Horizontal Gene Transfer; Immune system; Infection; Iowa; Iron; Laboratories; Lead; Life; Metabolic; Microbial Biofilms; Molecular; Organism; Pathogenesis; Penetration; Peptide Hydrolases; Physiological; Physiology; Positioning Attribute; Postdoctoral Fellow; Principal Investigator; Production; Proteins; Public Health; Publishing; Regulation; Research; Research Institute; Resistance; Role; Source; Staphylococcus aureus; System; Time; Universities; Work; antimicrobial; base; design; experience; extracellular; killings; mutant; novel therapeutics; quorum sensing; uptake

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）：主要研究员（Boles博士）目前是爱荷华大学的博士后研究员。 他在多种致病细菌物种中研究细菌生理学和生物膜发育的丰富经验。在接下来的12个月内，他计划在一家主要的研究所获得任期的学术职位，未来研究重点是了解金黄色葡萄球菌生理和发病机理。他的实验室的长期目标是了解从哺乳动物宿主蛋白中获得金黄色葡萄球菌获得的分子机制，以及这些宿主蛋白如何影响生物膜的形成和分散。拟议的研究将着重于阐明金​​黄色葡萄球菌如何从血红蛋白中获得血红素（因此是铁），并检查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。初步工作发现，金黄色葡萄球菌细胞外蛋白酶活性对于从血红蛋白和血红蛋白中获取铁是必需的，可能会影响金黄色葡萄球菌蛋白酶的产生。该提案的具体目的是设计为1）确定血红蛋白血红素链球菌的特定细胞外蛋白酶（S），2）定义血红蛋白对细胞外蛋白酶表达的调节作用，以及3）检查血红蛋白对血红蛋白链球菌链球菌对金果杆菌生物链球菌形成的影响。鲍尔斯博士的研究计划与公共卫生有很大的意义，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。 拟议项目的发现将增加对金黄色葡萄球菌致病机制的理解，并可能导致用于治疗金黄色葡萄球菌感染的新治疗选择。