Quorum signal eavesdropping by Moraxella catarrhalis

描述(申请人提供)：该项目旨在定义卡他莫拉氏菌(Mcat)如何感知其他生物产生的法定信号。MCAT是引起中耳炎和其他机会性呼吸道感染的主要因素之一，我们的数据表明，Mcat可以感应到流感嗜血杆菌产生的二羟基戊二酮(DPD)法定信号。我们假设Mcat“窃听”其他病原体产生的法定信号分子，导致Hag粘附素的产生增加，并随之而来的是生物被膜耐药性的增加。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摄取DPD的决定因素。具体目的2.明确DPD反应的决定因素。具体目的3.明确群体信号窃听在实验性中耳炎持续时间和毒性中的重要性。中耳炎是最常见的儿科传染病之一，影响大多数儿童，给总健康带来数十亿美元的损失。 每年的护理费用。显然，这些感染中有很大一部分是由麦卡特引起的，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药性细菌菌株不断出现的限制。这些研究的结果将为Mcat在代表大多数病例的多菌感染中持续存在的机制提供重要的洞察。这些见解可能是设计治疗慢性麦加特感染的新方法的关键进展。 与公共卫生相关：中耳炎是一种世界范围内常见且代价高昂的主要儿科疾病，每年造成的总经济影响高达数十亿美元。中耳炎感染是儿科就诊的主要原因，新的抗生素处方，以及外科注射鼓室引流管以缓解慢性和复发性中耳炎是美国最常见的外科手术，显然卡他莫拉菌是这些感染的主要原因。因此，提高对卡他毛虫生物学和致病机理的认识具有重要意义。

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. PUBLIC HEALTH RELEVANCE: Otitis media is a major common and costly pediatric illness worldwide, accounting for billions of dollars per year in total economic impact. Otitis media infections are the leading reason for pediatric office visits, new antibiotic prescriptions, and surgical instillation of tympanic drain tubes to relieve chronic and recurrent otitis media is the most commonly performed surgical procedure in the U.S. and it is clear that Moraxella catarrhalis is a major cause of these infections. It is thus of great importance to improve our knowledge of M. catarrhalis biology and pathogenesis.