Microbial interactions in otitis media

描述（由申请人提供）：本项目旨在确定多种微生物感染如何影响细菌性中耳炎的发展、严重程度和治疗。流感嗜血杆菌（Hi）是与中耳炎相关的主要细菌种类，我们的数据显示，同时感染多种Hi菌株是常见的。我们假设Hi菌株在生物膜群落中经历了种内和种间的群体信号和水平基因转移，从而影响了菌株多样性和毒力决定因素的水平传播。为了解决这些假设，我们将完成以下具体目标：了解具有不同产量和/或感应群体信号的Hi菌株之间的关系。在栗鼠感染模型中，不同的训练关系如何影响细菌持久性和疾病严重程度？定义同一生物膜群落内Hi毒株中毒力决定因素的出现和传播。中耳炎是最常见的儿科传染病之一，影响大多数儿童，每年的医疗保健费用总额达数十亿美元。很明显，这些感染中有很大一部分是由Hi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不同的Hi毒株在感染过程中如何竞争和/或合作提供重要的见解。此外，我们将获得关于新基因型如何在生物膜群落中出现和传播的重要新信息。这些发现将是深入了解持续性和毒性基本机制的关键步骤，这将是制定诊断、预防和/或治疗中耳炎感染的新策略所必需的。

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.