BLR&D Research Career Scientist Award Application

BLR

• 批准号: 10293577
• 负责人: Philip N. Rather
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10293577
• 关键词: Acinetobacter baumannii; Address; Afghanistan; Agar; Antibiotic Resistance; Antibiotics; Area; Attenuated; Award; Bacteria; Basic Science; Biochemical; Blood Circulation; Cell division; Cells; Collaborations; Defect; Development; Engineering; Fostering; Freedom; Frequencies; Funding; Gene Silencing; Genes; Genetic; Genetic Transcription; Goals; Gram-Negative Bacteria; Health; Hospitals; Human; Infection; Intervention; Iraq; Legal patent; Link; Mentors; Microbiology; Military Personnel; Mus; Nature; Phenotype; Population; Regulation; Research; Research Personnel; Research Project Grants; Resistance; Role; Scientist; Skin Tissue; Soft Tissue Infections; Soldier; Structure of parenchyma of lung; Training; Translational Research; United States Department of Veterans Affairs; United States National Institutes of Health; Universities; Urinary tract; Vaccinated; Vaccines; Virulence; Virulent; War; Work; World Health Organization; beta-Lactam Resistance; beta-Lactamase; beta-Lactams; career; injured; next generation; novel; novel strategies; novel therapeutics; operation; pathogen; post-doctoral training; programs; resistant strain; soft tissue; student training; transcriptomics

Project Summary. The Gram-negative bacterium Acinetobacter baumannii is a leading cause of infections in both the hospital setting and in military personnel injured during wartime. The goal of this Research Career Scientist Award is to continue addressing the mechanisms that regulate virulence and β−lactam resistance in A. baumannii. A high-frequency switch that regulates the transition between virulent (opaque) and avirulent (translucent) forms of A. baumannii will be studied using a combination of genetic and biochemical approaches. The role of a putative bistable transcriptional regulator in the opaque to translucent virulence switch will be investigated by genetic and transcriptomic approaches. A second area of research is focused on the regulation of intrinsic β-lactam resistance in A. baumannii. Our work has identified a novel gene in A. baumannii that is required for intrinsic β−lactam resistance. Inactivation of this gene sensitizes A. baumannii to β−lactams and also confers a prominent cell division defect. This provides the first link between defects in cell division and decreased intrinsic β-lactam resistance and suggests novel interventions that target cell division may sensitize cells to β-lactams. These research projects are highly collaborative and involve VA investigators at both the Atlanta VAMC and the Louis Stokes VAMC in Cleveland, OH. This project will continue to foster these collaborations and allow for the development of new projects. This project will also have an important training component, where mentoring for junior VA investigators will be provided. Lastly, student and postdoctoral training will continue to be an integral component of this research plan, with the goal of developing the next generation of VA scientists by mentoring a CDA-2 awarded project.

项目摘要。 革兰氏阴性细菌鲍曼不动杆菌是引起以下疾病的主要原因 医院环境和受伤军事人员中的感染 该研究职业科学家奖的目标是继续进行。 解决调节A中毒力和β-内酰胺耐药性的机制。 鲍曼不动杆菌是调节毒力之间过渡的高频开关。 （不透明）和无毒（半透明）形式的鲍曼不动杆菌将使用 遗传和生化方法的结合。 不透明到半透明毒力开关中的双稳态转录调节因子将 通过遗传和转录组学方法进行研究的第二个领域。 研究重点是A. 内在β-内酰胺抗性的调节。 我们的工作在鲍曼不动杆菌中发现了一个所需的新基因。 该基因的失活会使鲍曼不动杆菌变得敏感。 β-内酰胺，并且还赋予显着的细胞分裂缺陷。 细胞分裂缺陷与内在β-内酰胺减少之间的第一个联系 耐药性并提出针对细胞分裂可能致敏的新干预措施 细胞转化为β-内酰胺。 这些研究项目具有高度协作性并涉及 VA 亚特兰大 VAMC 和路易斯斯托克斯 VAMC 的调查员 俄亥俄州克利夫兰该项目将继续促进这些合作并允许 对于新项目的开发也将具有重要意义。 培训部分，将为初级 VA 调查员提供指导。 最后，学生和博士后培训将继续成为不可或缺的一部分 该研究计划的一部分，目标是开发下一代 VA 科学家通过指导 CDA-2 获奖项目。