Analysis of Novel Acinetobacter baumannii Adhesins

新型鲍曼不动杆菌粘附素的分析

• 批准号: 8549948
• 负责人: Anthony A Campagnari
• 金额: $ 18.62万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-26 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8549948
• 关键词: Accounting; Acinetobacter baumannii; Antibiotic Resistance; Bacillus (bacterium); Bacteremia; Bacteria; Bacterial Adhesins; Communities; Desiccation; Development; Devices; Disease Outbreaks; Disinfectants; Employee Strikes; Environment; Goals; Health care facility; Healthcare; Human; Immunocompromised Host; In Vitro; Incidence; Indwelling Catheter; Infection; Infection prevention; Investigation; Knowledge; Lead; Medical; Methods; Microbial Biofilms; Nosocomial Infections; Organism; Pathogenesis; Patients; Pneumonia; Reporting; Research; Resistance; Role; Staging; Structure; Surface; Testing; Time; Urinary tract infection; antimicrobial; design; in vivo; intercellular connection; novel; pathogen; prevent; response

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.

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著增加，约占所有医院获得性感染的1-3%，通常涉及免疫缺陷宿主。鲍曼不动杆菌也是设备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。偶尔有报道称鲍曼不动杆菌是严重的社区获得性肺炎和菌血症的罕见原因，尽管这些都是相当局部性的。也许比鲍曼不动杆菌发病率增加更令人不安的是，据报道，全球各地的许多设施中迅速出现了耐药菌株。这尤其令人不安，因为鲍曼不动杆菌已经显示出惊人的能力，能够在非生物表面生存并持续很长时间。尽管许多研究集中在鲍曼不动杆菌的耐药性上，但令人惊讶的是，很少有研究旨在确定耐药机制和致病的基本步骤。因此，我们对鲍曼不动杆菌在非生物表面停留、定殖和感染宿主的基本机制的了解有很大差距。这个应用程序的第一个目标是识别和表征 鲍曼不动杆菌在与非生物表面接触后表达的新型粘附素，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靶标。这项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致病中的作用。我们将在以下特定目标中测试假设：特定目标1：表征促进体外非生物表面附着、细胞间连接和生物膜形成的因素。明确新型黏附素(S)对鲍曼不动杆菌在体内的持久性和存活的作用。