Preventing Persistence and Spread of Acinetobacter baumannii in Hospitals

 描述(由申请人提供)：抗生素耐药率上升，医院获得性细菌感染，以及我们日益减少的抗生素选择，正在削弱所有医疗保健 需要在医院进行康复的治疗。了解细菌是如何在医院中持续和传播的，对于增加耐药医院相关细菌感染的负担至关重要。鲍曼不动杆菌是一种医院相关病原菌，重要性迅速增长，是临床地方性污染的典范。鲍曼不动杆菌地方性菌株在医院的反复暴发是有据可查的，它对各种医疗设备的定植以及从医院根除它的难度也是如此。鲍曼不动杆菌强大的脱水耐受性是加剧这些问题的一个关键特征，然而，描述干燥诱导鲍曼不动杆菌或任何细菌致死和存活的潜在机制的信息很少。这项建议的总体目标是确定氧化应激和蛋白平衡成分对脱水耐受性至关重要的作用。这项建议的具体目标是(1)表征干燥过程中氧化应激的作用并确定靶标，以及(2)表征促进干燥存活的鲍曼不动杆菌蛋白伴侣网络的成分。这些目标的完成将有助于为细菌在临床环境中的持久性提供基本的知识体系，并提供对鲍曼不动杆菌在干燥状态下长时间存活的机制的更好理解。这项建议代表了一种预防性的方法，以根除医院内病原菌的污染和传播，并将为未来对一种危重、 然而，对传染病控制方面的研究还很少。

 DESCRIPTION (provided by applicant): Increasing rates of antibiotic resistant, hospital-acquired bacterial infections, and our diminishing antibiotic options, are undercutting all medical treatments that require hospital-based recovery. Understanding how bacteria persist and spread in hospitals is paramount to elevating the burden of antibiotic resistant hospital-associated bacterial infections. Acinetobacter baumannii is a hospital-associated pathogen of rapidly growing importance, and is a paradigm for endemic clinical contamination. Reoccurring hospital outbreaks of endemic A. baumannii strains are well documented, as are its colonization of a wide array of medical equipment and the difficulty of exterminating it from hospitals. A. baumannii's robust desiccation tolerance is a key characteristic exacerbating each of these problems, however scarce information is available describing the underlying mechanisms of desiccation-induced lethality and survival for A. baumannii or any bacterium. The overall objectives of this proposal are to characterize the role of oxidative stress and proteostasis components critical for desiccation tolerance. The specific aims of this proposal are (1) to characterize the role and identify targets of oxidative stress during desiccation and (2) to characterize components of A. baumannii's protein chaperone network that promote desiccation survival. The completion of these aims will contribute to an essential body of knowledge to the persistence of bacteria in the clinical setting and provide a better understanding of the mechanisms by which A. baumannii survives for long periods of time in the desiccated state. This proposal represents a preventative approach to eradicating contamination and spread of pathogenic bacteria in hospitals and will offer a framework for future investigation of a critical, yet understudied, aspect of infectious disease control.