BLR&D Research Career Scientist Award Application

项目摘要。 革兰氏阴性菌鲍曼不动杆菌是导致 医院环境和军事人员中的感染， 战时这项研究职业科学家奖的目标是继续 解决调节A. 鲍曼不动杆菌。一种高频开关，调节有毒物质 （不透明）和无毒（半透明）形式的A。鲍曼不动杆菌将使用 遗传学和生物化学方法的结合。一个假定的角色 在不透明到半透明的毒力转换中， 通过遗传学和转录组学方法进行研究。的第二区域 研究集中在A. 鲍曼不动杆菌。我们的工作已经确定了一个新的基因在A。鲍曼不动杆菌 对β-内酰胺的内在耐药性。该基因的失活使A.鲍曼不 β-内酰胺类药物，也会导致明显的细胞分裂缺陷。这提供了以下 细胞分裂缺陷与内源性β-内酰胺减少之间的第一个联系 并提出了新的干预措施，靶细胞分裂可能敏化 细胞转化为β-内酰胺。 这些研究项目是高度合作和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 俄亥俄州克利夫兰该项目将继续促进这些合作，并允许 为新项目的开发。该项目还将具有重要的 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是一个不可或缺的 该研究计划的一部分，目标是开发下一代 通过指导一个CDA-2获奖项目，

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.