Analysis of Novel Acinetobacter baumannii Adhesins

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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.