Microbial interactions in otitis media

中耳炎中的微生物相互作用

• 批准号: 9338965
• 负责人: David Arnold Ornelles
• 金额: $ 36.4万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9338965
• 关键词: Accounting; Address; Affect; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Antibiotic Resistance; Biology; Child; Childhood; Chinchilla (genus); Chronic; Clinical Research; Communicable Diseases; Communities; Data; Development; Diagnosis; Diffusion; Disease; Epidemiologic Studies; Funding; Genetic; Genotype; Goals; Growth; Haemophilus influenzae; Health; Health Care Costs; Horizontal Gene Transfer; Incidence; Individual; Infection; Kinetics; Knowledge; Learning; Licensing; Light; Medical center; Microbial Biofilms; Modeling; Moraxella (Branhamella) catarrhalis; Mutation; Office Visits; Operative Surgical Procedures; Organism; Otitis Media; Oxidative Stress; Pathogenesis; Patients; Prevention; Production; Recurrence; Reporting; Resistance; Role; Severities; Severity of illness; Signal Transduction; Streptococcus pneumoniae; Structure; Time; Training; Tube; Tympanostomy; Vaccines; Virulence; Work; base; beta-Lactamase; co-infection; economic impact; experience; forest; improved; in vivo; insight; microorganism interaction; novel strategies; pathogen; prevent; quorum sensing; uptake

DESCRIPTION (provided by applicant): This project aims to define how polymicrobial infection impacts the development, severity, and treatment of bacterial otitis media. Haemophilus influenzae (Hi) is the leading bacterial species associated with otitis media, and our data show that coinfection with multiple strains of Hi is common. We hypothesize that strains of Hi undergo intrastrain and interstrain quorum signaling and horizontal gene transfer within biofilm communities which impacts strain diversity and horizontal dissemination of virulence determinants. In order to address these hypotheses we will complete the following Specific Aims: Specific Aim 1. To understand relationships between Hi strains with differing production and/or sensing of quorum signal Specific Aim 2. To ask how different inters train relationships affect bacterial persistence and disease severity in the chinchilla infection model Specific Aim 3. To define emergence and dissemination of virulence determinants among Hi strains within the same biofilm community. Otitis media is among the most common pediatric infectious diseases, affecting the majority of children and accounting for billions of dollars in ttal health-care costs per year. It is clear that a significant proportion of these infections are cause by Hi, 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 how different Hi strain act competitively and/or cooperatively during infection. Moreover, we will gain significant new information regarding how new genotypes emerge and are disseminated within a biofilm community. These findings will be crucial steps in gaining the deep understanding of basic mechanisms for persistence and virulence that will be necessary for tailoring new strategies for diagnosis, prevention, and/or therapy of otitis media infections.

描述（由申请人提供）：该项目旨在定义多数菌感染如何影响细菌性中耳炎的发育，严重程度和治疗。流感嗜血杆菌（HI）是与中耳炎有关的主要细菌物种，我们的数据表明，与多种HI菌株共同感染很常见。我们假设HI的菌株经历了生物膜群落内的局部内部和环间群体信号传导和水平基因转移，这会影响毒力决定因素的应变多样性和水平传播。为了解决这些假设，我们将完成以下特定目的：特定目的1。了解与群体信号特定目的不同的HI菌株之间的关系和/或感知/或感应的方案特定目的2。询问不同的相互关系如何影响细菌持久性和疾病的严重程度，而丁香感染感染模型的特定目标3。在较高的人群中定义了与互联性相同的互联性确定性的互联性。中耳炎是最常见的小儿传染病之一，影响了大多数儿童，并且每年占数十亿美元的TTAL医疗保健费用。显然，这些感染中很大一部分是由HI引起的，目前尚无许可疫苗。不幸的是，我们治疗这些感染的能力越来越受抗生素耐药细菌菌株的持续出现。这些研究的结果将为您的HI菌株在感染过程中的竞争性和/或合作的作用如何提供重大见解。此外，我们将获得有关如何在生物膜社区中出现新基因型和传播新基因型的重要新信息。这些发现将是对持久性和毒力的基本机制深入了解的关键步骤，这对于调整诊断，预防和/或治疗中耳炎媒体感染的新策略是必不可少的。