Understanding the role of CsrA in Acinetobacter baumannii survival and infection

摘要 鲍曼不动杆菌是一种能引起严重感染的条件致病菌。 由于多药耐药，这些疾病很难治疗。这些感染中的大多数 发生在住院、危重病人中，并在医院环境中传播是一种 对这种病原体的主要关注。我们开发了一种屏幕来识别支持 鲍曼弧菌在干燥表面的生存能力，因为这种能力可能有助于鲍曼弧菌 散开。我们发现的其中一个基因编码调节蛋白CSRA。这个调整器是 对于控制其他细菌物种的新陈代谢和毒性很重要，正如我们一开始 为了研究CSRA在鲍曼不动杆菌中的功能，我们发现它似乎对 与主机相关的增长。这为发现新的基因和 通过进一步研究鲍曼不动杆菌毒力和传播的决定因素 CSRA在该生物体中的调节功能。这项建议的目标是：1)确定 通过研究CSRA在控制寄主相关生长中的作用来研究寄主相关生长所需的特定功能 以及2)确定CSRA的直接调控靶点，以便 了解它如何影响鲍曼假丝酵母的生长和环境生存。长期的 这项研究的目标是确定新的开发的潜在目标 治疗鲍曼不动杆菌感染，并更好地了解其机制 通过它鲍曼不动杆菌在医院环境中坚持，目标是发展 新的干预措施，以遏制其在医院的传播。

Abstract Acinetobacter baumannii is an opportunistic pathogen that causes serious infections which are very difficult to treat due to multidrug resistance. The majority of these infections occur in hospitalized, critically ill individuals, and spread through the hospital environment is a major concern for this pathogen. We developed a screen to identify genes that support the survival of A. baumannii on dry surfaces, since this ability likely facilitates A. baumannii’s spread. One of the genes we identified encodes the regulatory protein CsrA. This regulator is important for controlling metabolism and virulence in other bacterial species, and as we began to study the function of CsrA in A. baumannii, we found that it also appeared to be critical for host-associated growth. This has provided a great opportunity to discover novel genes and determinants involved in A. baumannii virulence and spread by further investigating the regulatory function of CsrA in this organism. The goals of this proposal are: 1) To determine the specific functions needed for host-associated growth by examining role of CsrA in controlling A. baumannii metabolism; and 2) To identify direct regulatory targets of CsrA in order to understand how it influences A. baumannii growth and environmental survival. The long-term objectives of this research are to identify potential targets for the development of new treatments for A. baumannii infections, and to gain a better understanding of the mechanisms through which A. baumannii persists in the nosocomial environment with the goal of developing new interventions to curb its spread in hospitals.