Microbial interactions in otitis media

描述（由申请人提供）：本项目旨在确定多微生物感染如何影响细菌性中耳炎。流感嗜血杆菌（Hi）、肺炎链球菌（Sp）和卡他莫拉菌（Mcat）是OM患者的主要分离株，大量证据表明OM通常涉及这些微生物的组合。我们假设细菌物种之间的相互作用可以影响OM疾病参数，包括细菌持久性，对清除和抗生素治疗的耐药性，以及宿主炎症反应的开始，进展和严重程度。为了解决这一假设，我们将完成以下具体目标：具体目标1：确定引起OM的细菌病原体之间的相互作用。具体目标2：探讨不同的种间关系如何影响实验OM。特异性目的3：评价多微生物感染对抗生素耐药性的影响。目的4：了解鼓膜造瘘患者合并感染的发生率。我们目前关于细菌发病机制的大部分知识来自于使用纯培养物的感染研究，这可能不能完全代表感染如何在实际患者中发生。这一建议提供了一个机会来了解居住在同一生态位的多种病原体如何在对持续感染至关重要的生物膜群落中相互影响。公共卫生相关性：中耳炎是世界范围内一种主要的常见和昂贵的儿科疾病，每年的经济影响总额达数十亿美元。中耳炎感染是儿科就诊的主要原因，新的抗生素处方和通过手术植入鼓室引流管来缓解慢性和复发性中耳炎是美国最常见的外科手术。流感嗜血杆菌、肺炎链球菌和卡他莫拉菌长期以来被认为是引起中耳炎的最常见细菌。现在很清楚，许多这些感染涉及同时感染不止一种生物体。该应用程序的重点是了解这些细菌物种如何在生物膜群落中相互作用，这是细菌在体内持久性的主要决定因素。了解细菌如何形成这些生物膜将是学习更好地诊断、预防和/或治疗慢性感染的重要一步。

DESCRIPTION (provided by applicant): This project aims to define how polymicrobial infection influences bacterial otitis media. Haemophilus influenzae (Hi), Streptococcus pneumoniae (Sp), and Moraxella catarrhalis (Mcat) are the predominant isolates from patients with OM, and a wealth of evidence indicates that OM often involves combinations of these organisms. We hypothesize that interactions between bacterial species can impact OM disease parameters that include bacterial persistence, resistance to clearance and antibiotic treatment, and the initiation, progression and severity of the host inflammatory response. In order to address this hypothesis we will complete the following Specific Aims: Specific Aim 1: To define interactions among bacterial pathogens causing OM. Specific Aim 2: To ask how different interspecies relationships affect experimental OM. Specific Aim 3: To evaluate impact of polymicrobial infection on antibiotic resistance. Specific Aim 4: To establish the incidence of coinfection in patients undergoing tympanostomy. Most of our current knowledge about bacterial pathogenesis is derived from infection studies using pure cultures that may not fully represent how infections occur in actual patients. This proposal presents an opportunity to learn how multiple pathogens inhabiting the same ecological niche influence one another in biofilm communities that are critical to persistent 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. Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis have long been recognized as the most common bacterial causes of otitis media, and it is now clear that many of these infections involve simultaneous infection with more than one organism. The focus of this application is to understand how these bacterial species interact in the biofilm communities that are a major determinant of bacterial persistence in vivo. Understanding how bacteria form these biofilms will be an important step in learning to better diagnose, prevent, and/or treat chronic infections.