Patient-Oriented Research on Hospital-Acquired Pathogens

以患者为中心的医院获得性病原体研究

基本信息

批准号：
8698709
负责人：
ALAN R HAUSER
金额：
$ 10万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-10 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8698709
关键词：
Accounting Acinetobacter baumannii Acute Pneumonia Address Animal Model Area Award Bacteria Bacterial Typing Biological Assay Blood Circulation Cells Clinical Collection Cytosol Data Development Disease Doctor of Philosophy Elements Environment Epithelial Epithelial Cells Fostering Funding Genes Genetic Genetic Materials Genome Genomics Goals Heterogeneity Hospitals Human Immune system In Vitro Infection Injection of therapeutic agent Link Lung Mediating Mentors Mentorship Mid-Career Clinical Scientist Award (K24)Modeling Needles Nosocomial pneumonia Open Reading Frames Outcome Pathogenesis Patients Phagocytes Pneumonia Properdin Proteins Pseudomonas aeruginosa Research Research Activity Research Personnel Research Support Role Source Structure System Testing Time Toxin Training Type III Secretion System Pathway Universities Validation Variant Ventilator Virulence Virulence Factors Virulent Wages Work arm base cell type enhancing factor genetic element genome sequencing improved in vivo killings mouse model neutrophil novel pathogen patient oriented research prognostic programs public health relevance skills

项目摘要

DESCRIPTION (provided by applicant): This K24 application provides 33% salary support to Dr. Hauser to allow him to mentor MD or MD/PhD fellows, improve his mentorship skills, and pursue patient-oriented research in the area of hospital-acquired bacterial pathogens. In particular, this award will allow him to continue current research on the role of Pseudomonas aeruginosa type III secretion in the progression of pneumonia. Bacterial type III secretion systems form needle-like structures that inject toxins called "effector proteins" directly into the cytosol of host cells. The goal of this study is to determine how P. aeruginosa wields effector proteins in vivo to cause severe pneumonia. The focus will be on interactions between the host innate immune system and effector proteins. The relevance of these findings will be confirmed in human patients infected with P. aeruginosa. In addition to expediting current research, this award will allow Dr. Hauser to expand his research into a new area. Approaches used in the past to address the question of why some P. aeruginosa strains are more virulent than others will now be applied to another hospital-acquired pathogen: Acinetobacter baumannii. Accessory genomic elements (genetic material found in some strains but not in others) will be identified that encode pathogenic factors and enhance the virulence of strains containing them. These markers for hypervirulent strains will be validated in human patients with A. baumannii infections. Both these projects further characterize disease mechanism by utilizing studies involving face-to-face contact with patients. They are thus ideal training vehicles for junior clinician investigators. In summary, this K24 award will provide salary support and research funds to allow Dr. Hauser to spend more of his time mentoring clinical fellows in patient-oriented research, to expand his patient-oriented research activities, and to enhance his mentoring skills.

描述（由申请人提供）：此K24申请为Hauser博士提供了33％的薪水支持，以使他能够指导MD或MD/PHD研究员，提高他的指导能力，并在医院获得的细菌病原体领域进行以患者为导向的研究。特别是，该奖项将使他能够继续研究铜绿假单胞菌III型在肺炎进展中的作用。细菌III型分泌系统形成类似针的结构，将毒素直接注入称为“效应蛋白” 宿主细胞的细胞质。这项研究的目的是确定铜绿假单胞菌如何在体内发挥效应蛋白来引起严重的肺炎。重点将放在宿主先天免疫系统和效应子蛋白之间的相互作用上。这些发现的相关性将在感染铜绿假单胞菌的人类患者中得到证实。除了加快目前的研究之外，该奖项还将使豪瑟博士能够将其研究扩展到一个新领域。过去使用的方法解决了为什么某些铜绿假单胞菌菌株比其他铜质菌株更具毒性，现在将应用于另一种医院获得的病原体：鲍曼尼杆菌杆菌。将确定辅助基因组元素（在某些菌株中发现的遗传物质，但在另一些菌株中发现），这些元素将被鉴定出编码致病因素并增强含有菌株的毒力的毒力。这些高呼吸菌株的标记物将在鲍曼尼曲霉感染的人类患者中得到验证。这两个项目通过利用涉及与患者面对面接触的研究进一步表征了疾病机制。因此，它们是初级临床研究人员的理想训练车。总而言之，该K24奖将提供薪水支持和研究资金，以使Hauser博士在以患者为导向的研究中花费更多的时间指导临床研究员，以扩大他的以患者为导向的研究活动并提高他的指导能力。