BLR&D Research Career Scientist Award Application

项目摘要。 革兰氏阴性杆菌鲍曼不动杆菌是引起 医院环境和军事人员受伤期间的感染 战时。这项研究职业科学家奖的目标是继续 阐述了A.菌株毒力和β−内酰胺类耐药性的调控机制。 鲍曼尼。一种高频开关，调节毒力之间的转换 (不透明)和无毒(半透明)鲍曼不动杆菌将使用 基因和生化方法的结合。推定人的角色 双稳态转录调控因子在不透明到半透明的毒力转换中会 通过遗传学和转录组学方法进行研究。第二个领域 研究的重点是调节根癌农杆菌对β-内酰胺类内酰胺类抗生素的抗性。 鲍曼尼。我们的工作已经在鲍曼不动杆菌中发现了一种新的基因，它需要 对于固有的β−内酰胺类耐药。该基因的失活使鲍曼不动杆菌变得敏感 对β−内酰胺类药物也具有显著的细胞分裂缺陷。这提供了 细胞分裂缺陷与固有β-内酰胺减少之间的第一个联系 并提出了针对细胞分裂的新干预措施，可能会使人变得敏感 细胞对β-内酰胺类药物。 这些研究项目高度协作，涉及退伍军人事务部 亚特兰大VAMC和路易斯·斯托克斯VAMC的调查人员都在 俄亥俄州克利夫兰该项目将继续促进这些合作，并允许 用于开发新项目。这个项目还将有一个重要的 培训部分，将为退伍军人管理局初级调查员提供指导。 最后，学生和博士后培训将继续是一个不可或缺的组成部分 这项研究计划的组成部分，目标是开发下一代 通过指导CDA-2获奖项目，获得退伍军人管理局科学家的支持。

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.