Pathophysiology of Staphylococcus aureaus Necrotizing Pneumonia and Severe Sepsis

金黄色葡萄球菌坏死性肺炎和严重脓毒症的病理生理学

基本信息

批准号：
8106296
负责人：
Christopher Montgomery
金额：
$ 12.57万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-18 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8106296
关键词：
Animal Disease Models Arginine Bacteriology Basic Science Biological Assay Chicago Child Childhood Clinical Communicable Diseases Communities Critical Care Detection Discipline Disease Elements Epidemic Ethics Evaluation Fibrinogen Functional disorder Gene Expression Gene Proteins Genes Genetic Genus staphylococcus Healthcare Hemolysin Human In Vitro Indium Infection Investigation Journals Laboratories Light Locales Mentors Methods Modeling Molecular Biology Molecular and Cellular Biology Northern Blotting Panton-Valentine leukocidin Pathogenesis Phenotype Pneumonia Process Production Rattus Regulator Genes Regulatory Element Relative (related person)Research Research Personnel Reverse Transcriptase Polymerase Chain Reaction Role Sampling Scientist Sepsis Staphylococcus aureus Syndrome System Techniques Testing Time Toxin Training Universities Up-Regulation Virulence Virulence Factors Virulent Work comparative experience in vivo insight instructor methicillin resistant Staphylococcus aureus mutant pathogen programs skills success

项目摘要

DESCRIPTION (provided by applicant): In this mentored clinical scientist training proposal, the applicant will test the hypothesis that expression of global regulatory elements and virulence factors differs among various pulsotypes of methicillin-resistant Staphylococcus aureus (MRSA) and that increased expression of key genes will correlate with virulence in an established rat model of necrotizing pneumonia. In addition, gene expression will be evaluated using an in vivo assay and compared to expression seen in vitro. S. aureus isolates causing community-associated (CA-MRSA) disease will be compared with isolates causing health-care-associated (HA-MRSA) disease. These studies will provide an excellent opportunity for training in molecular biology, bacteriology, and utilization of animal models of disease. The applicant, Christopher P. Montgomery, MD, is an Instructor in the Section of Pediatric Critical Care at the University of Chicago. He formally entered the laboratory of Robert S. Daum, MD, in February 2006, with effort interdigitated with ongoing clinical responsibilities. Dr. Montgomery is in the process of acquiring additional basic science training and has developed a rat model of CA-MRSA necrotizing pneumonia and severe sepsis. The proposed training plan provides 80% protected time, exceptional opportunities to acquire new skills and experience in cellular and molecular biology, as well as didactic training in laboratory techniques and ethical research conduct. The plan also provides interactions with a number of experienced investigators across disciplines, facilitating Dr. Montgomery's transition into successful independent investigation and competitiveness for independent R01 support. CA-MRSA is an important human pathogen causing a variety of severe clinical syndromes, including necrotizing pneumonia and severe sepsis in previously healthy children. Emphasis will be placed on evaluating the differences between the S. aureus genetic background USA300, the dominant circulating CA- MRSA strain in the U.S., and USA400, which it replaced. Insight into the virulence mechanisms of USA300 will shed light on its success in the community.

描述（由申请人提供）：在此指导性临床科学家培训计划中，申请人将测试以下假设：耐甲氧西林金黄色葡萄球菌 (MRSA) 的各种脉冲型之间的全局调节元件和毒力因子的表达存在差异，并且关键基因的表达增加将与已建立的坏死性肺炎大鼠模型中的毒力相关。此外，将使用体内测定评估基因表达，并与体外观察到的表达进行比较。引起社区相关 (CA-MRSA) 疾病的金黄色葡萄球菌分离株将与引起医疗保健相关 (HA-MRSA) 疾病的分离株进行比较。这些研究将为分子生物学、细菌学和疾病动物模型的利用提供绝佳的机会。申请人克里斯托弗·蒙哥马利（Christopher P. Montgomery）医学博士是芝加哥大学儿科重症监护科的讲师。他于 2006 年 2 月正式进入医学博士 Robert S. Daum 的实验室，一边努力一边承担持续的临床职责。 Montgomery 博士正在接受额外的基础科学培训，并开发了 CA-MRSA 坏死性肺炎和严重败血症的大鼠模型。拟议的培训计划提供 80% 的保护时间、获得细胞和分子生物学新技能和经验的绝佳机会，以及实验室技术和伦理研究行为的教学培训。该计划还提供与一些经验丰富的跨学科研究人员的互动，促进 Montgomery 博士过渡到成功的独立调查和独立 R01 支持的竞争力。 CA-MRSA 是一种重要的人类病原体，可引起多种严重的临床综合征，包括先前健康儿童的坏死性肺炎和严重败血症。重点将放在评估金黄色葡萄球菌遗传背景 USA300（美国主要循环 CA-MRSA 菌株）和它所取代的 USA400 之间的差异。对 USA300 毒力机制的深入了解将有助于了解其在社区中的成功。