Analysis of Novel Acinetobacter baumannii Adhesins

描述（由申请人提供）：鲍曼不动杆菌是一种革兰氏阴性杆菌，以引起卫生保健相关感染而闻名。在过去十年中，鲍曼不动杆菌感染显著增加，约占所有医院获得性感染的1-3%，通常涉及免疫功能低下的宿主。鲍曼不动杆菌也是器械相关感染的主要原因，如插管患者的肺炎和留置导尿管患者的尿路感染。偶尔有报道表明鲍曼不对称杆菌是引起严重社区获得性肺炎和菌血症的不常见原因，尽管这些都是相当局部的。也许比鲍曼不动杆菌发病率增加更令人不安的是，在全球许多设施中报告的抗生素耐药分离株的迅速出现。这尤其令人不安，因为鲍曼不动杆菌已经显示出一种惊人的能力，可以在非生物表面长时间生存和持续。尽管大量的研究都集中在鲍曼不动杆菌的抗生素耐药性上，但令人惊讶的是，很少有研究致力于确定其持续存在的机制和发病的基本步骤。因此，我们对鲍曼不动杆菌在非生物表面持续存在并定植和感染宿主的基本机制的了解存在重大差距。这个应用程序的第一个目标是识别和描述

DESCRIPTION (provided by applicant: Acinetobacter baumannii is a Gram-negative bacillus best known for causing health-care associated infections. Over the past decade infections with A. baumannii have increased significantly accounting for approximately 1-3% of all hospital-acquired infections usually involving immunocompromised hosts. A.baumannii is also a leading cause of device-associated infections such as pneumonia in intubated patients and urinary tract infections in patients with indwelling catheters. There have been occasional reports implicating A. baumannii as an uncommon cause of severe community-acquired pneumonia and bacteremia although these have been fairly localized. Perhaps more disturbing than the increase in A.baumannii incidence is the rapid emergence of antibiotic resistant isolates reported in numerous facilities around the globe. This is particularly troubling because A. baumannii has demonstrated a striking ability to survive and persist on abiotic surfaces for extended periods of time. Despite numerous efforts that focus on A. baumannii antibiotic resistance there are surprisingly few research efforts designed to identify mechanisms of persistence and essential steps of pathogenesis. Thus there is a significant gap in our knowledge of the basic mechanisms utilized by A. baumannii to persist on abiotic surfaces and to colonize and infect the host. The first goal of this application is to identify and characterize novel adhesins expressed by A. baumannii in response to contact with abiotic surfaces, to define the role of these structures in biofilm formation and determine if these surface structures represent attractive targets for eradication of environmental reservoirs. The second goal of this application is to determine the role of these surface structures in A. baumannii pathogenesis in vivo. We will test out hypotheses in the following specific aims: Specific Aim 1: Characterize the factors that promote attachment to abiotic surfaces, intercellular connections and biofilm formation in vitro. Specific Aim 2. Define the role of novel adhesin(s) to A. baumannii persistence and survival in vivo. PUBLIC HEALTH RELEVANCE: The ability of Acinetobacter baumannii to resist desiccation and disinfectants is one of the primary reasons this organism remains a major cause of nosocomial infections worldwide. This ability to survive on abiotic surfaces and medically relevant materials is directly related to significant outbreaks in healthcare facilities. The goalsof this research are to determine the bacterial factors expressed by A. baumannii that promote biofilm formation and to determine the role of these components in bacterial persistence and pathogenesis.