Analysis of Novel Acinetobacter baumannii Adhesins

描述（由申请方提供）：鲍曼不动杆菌是一种革兰氏阴性杆菌，以引起医疗相关感染而闻名。在过去的十年中，A.鲍曼不动杆菌显著增加，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管患者的尿路感染。偶尔有报道称A.鲍曼不动杆菌是严重的社区获得性肺炎和菌血症的一种罕见原因，尽管这些已经相当局部化。也许比鲍曼不动杆菌发病率的增加更令人不安的是，在地球仪的许多设施中报告了抗生素耐药分离株的迅速出现。这一点尤其令人担忧，因为A。鲍曼不动杆菌已经显示出在非生物表面上长时间存活和持续的惊人能力。尽管有许多努力集中在A。鲍曼不动杆菌抗生素耐药性令人惊讶的是，很少有旨在鉴定持久性机制和发病机理的基本步骤的研究工作。因此，我们对A.鲍曼不动杆菌能够在非生物表面上存活并定殖和感染宿主。此应用程序的第一个目标是识别和表征 A.以确定这些结构在生物膜形成中的作用，并确定这些表面结构是否代表根除环境储库的有吸引力的目标。本申请的第二个目标是确定这些表面结构在A.体内鲍曼不动杆菌致病机理。我们将在以下具体目标中检验假设：具体目标1：表征促进附着于非生物表面、细胞间连接和体外生物膜形成的因素。具体目标2。定义新粘附素对A.鲍曼不动杆菌在体内的持久性和存活率。 公共卫生相关性：鲍曼不动杆菌抵抗干燥和消毒剂的能力是该微生物仍然是全球医院感染的主要原因之一。这种在非生物表面和医学相关材料上生存的能力与医疗设施中的重大疫情直接相关。本研究的目的是确定A.鲍曼不动杆菌，促进生物膜形成，并确定这些成分在细菌持久性和发病机制中的作用。

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.