Quorum signal eavesdropping by Moraxella catarrhalis

卡他莫拉氏菌窃听群体信号

• 批准号: 8604707
• 负责人: WILLIAM E SWORDS
• 金额: $ 31.45万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-07 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8604707
• 关键词: Accounting; Address; Affect; Antibiotic Resistance; Antibiotics; Bacterial Adhesins; Bacterial Antibiotic Resistance; Biochemical; Biology; Child; Childhood; Chronic; Communicable Diseases; Data; Eustachian Tube; Family; Functional disorder; Genetic; Genetic Determinism; Haemophilus influenzae; Health Care Costs; Human; Infection; Knowledge; Licensing; Mediating; Microbial Biofilms; Moraxella (Branhamella) catarrhalis; Nature; Office Visits; Operative Surgical Procedures; Organism; Otitis Media; Pathogenesis; Production; Property; Protein Biosynthesis; Proteins; Recurrence; Regulation; Resistance; Role; Signal Transduction; Signaling Molecule; Testing; Tube; Vaccines; Virulence; base; design; economic impact; improved; in vivo; insight; middle ear; mutant; pathogen; quorum sensing; response; uptake

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.

描述（由申请人提供）：本项目旨在确定卡他莫拉菌（Mcat）如何感知其他生物产生的群体信号。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，我们的数据显示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”由其他病原体产生的群体信号分子，导致Hag粘附素的产生增加，并伴随着生物膜抗性特性的增加。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。 具体目标2。目的：明确影响Mcat DPD反应的决定因素。 具体目标3。目的：明确实验性中耳炎中群体信号窃听在Mcat持续性和毒力中的重要性。 中耳炎是最常见的儿科感染性疾病之一，影响大多数儿童，并占数十亿美元的总健康 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微生物感染中的持久性机制提供重要的见解。这些见解可能是设计治疗慢性Mcat感染的新方法的关键进展。