Analysis of Novel Acinetobacter baumannii Adhesins

新型鲍曼不动杆菌粘附素的分析

基本信息

批准号：
8355014
负责人：
Anthony A Campagnari
金额：
$ 23.78万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-26 至 2014-08-31
项目状态：
已结题

项目摘要

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.

描述（由申请人提供：鲍曼不动杆菌是一种革兰氏阴性杆菌，以引起医疗保健相关感染而闻名。在过去十年中，鲍曼不动杆菌感染显着增加，通常约占所有医院获得性感染的 1-3%鲍曼不动杆菌也是导致插管患者肺炎和留置导尿管患者尿路感染等设备相关感染的主要原因。有报道称鲍曼不动杆菌是严重社区获得性肺炎和菌血症的罕见原因，尽管这些情况相当局部化，但也许比鲍曼不动杆菌发病率的增加更令人不安的是全球许多设施中报告的抗生素耐药菌株的迅速出现。这尤其令人不安，因为鲍曼不动杆菌已表现出在非生物表面上长时间生存和持续的惊人能力。尽管针对鲍曼不动杆菌抗生素耐药性做出了许多努力，但令人惊讶的是，很少有研究工作旨在确定持久性机制和发病机制的基本步骤。因此，我们对鲍曼不动杆菌在非生物表面持续存在以及定植和感染宿主的基本机制的了解存在重大差距。该应用程序的首要目标是识别和表征鲍曼不动杆菌响应与非生物表面的接触而表达的新型粘附素，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了根除环境水库的有吸引力的目标。该应用的第二个目标是确定这些表面结构在鲍曼不动杆菌体内发病机制中的作用。我们将测试以下具体目标的假设：具体目标 1：描述促进非生物表面附着、细胞间连接和体外生物膜形成的因素。具体目标 2. 定义新型粘附素对鲍曼不动杆菌体内持久性和存活的作用。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生物体仍然是全球医院感染主要原因的主要原因之一。这种在非生物表面和医学相关材料上生存的能力与医疗机构中的重大疫情爆发直接相关。本研究的目的是确定鲍曼不动杆菌表达的促进生物膜形成的细菌因子，并确定这些成分在细菌持久性和发病机制中的作用。