Quorum signal eavesdropping by Moraxella catarrhalis

描述（由申请人提供）：该项目旨在确定卡他莫拉菌（Mcat）如何感知其他生物体产生的群体信号。 Mcat 是引起中耳炎和其他机会性气道感染的主要病原体之一，我们的数据表明，Mcat 可以感知流感嗜血杆菌产生的二羟基戊二酮 (DPD) 群体信号。我们假设 Mcat“窃听”其他病原体产生的群体信号分子，导致 Hag 粘附素产量增加，并随之增加生物膜抗性。为了解决这一假设，我们将完成以下具体目标： 具体目标 1：确定 Mcat 吸收 DPD 的决定因素。 具体目标 2. 定义 Mcat 中 DPD 响应的决定因素。 具体目标 3. 确定群体信号窃听对于实验性中耳炎期间 Mcat 持久性和毒力的重要性。 中耳炎是最常见的儿科传染病之一，影响大多数儿童，造成健康总额数十亿美元 每年的护理费用。很明显，这些感染中有很大一部分是由 Mcat 引起的，目前还没有获得许可的疫苗。不幸的是，我们治疗这些感染的能力越来越受到抗生素耐药菌株的不断出现的限制。这些研究的结果将为了解 Mcat 在代表大多数病例的多种微生物感染中持续存在的机制提供重要的见解。这些见解可能是设计治疗慢性 Mcat 感染新方法的关键进展。

DESCRIPTION (provided by applicant): This project aims to define how Moraxella catarrhalis (Mcat) senses quorum signals produced by other organisms. Mcat is among are the predominant agents causing otitis media and other opportunistic airway infections, and our data show that Mcat can sense dihydroxypentanedione (DPD) quorum signals produced by Haemophilus influenzae. We hypothesize that Mcat "eavesdrops" on quorum signal molecules produced by other pathogens, resulting in increased production of the Hag adhesin and concomitant increases in biofilm resistance properties. In order to address this hypothesis we will complete the following Specific Aims: Specific Aim 1: To identify determinants of DPD uptake by Mcat. Specific Aim 2. To define the determinants of DPD response in Mcat. Specific Aim 3. To define importance of quorum signal eavesdropping in Mcat persistence and virulence during experimental otitis media. Otitis media is among the most common pediatric infectious diseases, affecting the majority of children and accounting for billions of dollars in total health care costs per year. It is clear that a significant proportion of these infections are caused by Mcat, for which there is no currently licensed vaccine. Unfortunately, our ability to treat these infections is increasingly limited by the continued emergence of antibiotic-resistant bacterial strains. The results of these studies will provide significant insight into mechanisms for the persistence of Mcat in the polymicrobial infections that represent the majority of cases. Such insights could be pivotal advances in the design of new means for treatment of chronic Mcat infections.