Microbial interactions in otitis media

描述(由申请者提供)：该项目旨在定义多菌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患者的主要病原菌，大量证据表明OM往往是这些细菌的组合。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抵抗力，以及宿主炎症反应的启动、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：探讨不同种间关系对实验性OM的影响。具体目的3：评价多菌感染对抗生素耐药性的影响。具体目标4：建立鼓室造口术患者合并感染的发生率。我们目前关于细菌发病机制的大多数知识都来自于使用纯培养的感染研究，这些培养可能不能完全代表实际患者中感染是如何发生的。这一建议提供了一个机会，以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。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。长期以来，流感嗜血杆菌、肺炎链球菌和卡他莫拉菌一直被认为是导致中耳炎的最常见细菌原因，现在很明显，这些感染中的许多涉及多个微生物的同时感染。这一应用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，生物膜群落是细菌在体内持久性的主要决定因素。了解细菌是如何形成这些生物膜的，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.