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

• 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
• 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

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.

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.此外，将使用体内测定法评估基因表达，并与体外表达进行比较。将导致社区相关（CA-MRSA）疾病的金黄色葡萄球菌分离株与引起医疗保健相关（HA-MRSA）疾病的分离株进行比较。这些研究将为培训分子生物学，细菌学和疾病动物模型的利用提供一个绝佳的机会。 申请人克里斯托弗·P·蒙哥马利（Christopher P.他于2006年2月正式进入马里兰州罗伯特·杜姆（Robert S.蒙哥马利博士正在获取其他基础科学培训的过程中，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了80％的受保护时间，出色的机会，可以获取细胞和分子生物学方面的新技能和经验，以及实验室技术和道德研究行为的教学培训。该计划还与跨学科的许多经验丰富的研究人员提供了互动，从而促进了蒙哥马利博士向独立R01支持的成功独立调查和竞争力的过渡。 CA-MRSA是引起各种严重临床综合征的重要人类病原体，包括肺炎坏死性肺炎和严重的败血症。将重点放在评估金黄色葡萄球菌遗传背景USA300，美国的主要循环CA-MRSA菌株和USA400的差异上。对USA300的毒力机制的洞察力将阐明其在社区中的成功。