Bacterial biofilms in otitis media

描述（由申请人提供）：本申请旨在对R 01项目进行竞争性更新，该项目的重点是确定中耳炎感染期间生物膜中细菌持久性的决定因素。中耳炎是由气道阻塞引起的，如流感嗜血杆菌（Hi），它形成生物膜群落，促进中耳腔内的细菌持久存在。在最初的四年支持期间，我们已经定义了Hi生物膜形成的机制，并证明了生物膜促进细菌在体内的持久性。在下一个项目期间，我们将确定生物膜对宿主清除的抗性的决定因素。我们假设，生物膜促进细菌抵抗清除，因为激活的细菌应激反应内的生物膜，和固有的抵抗宿主吞噬细胞。为了解决这些假设，我们将完成以下具体目标：具体目标1：描述实验性中耳炎期间细菌应激反应在Hi持续性中的作用。 具体目标2：确定Hi生物膜对吞噬细胞和细胞外杀伤的抗性。 虽然很明显，生物膜的生长模式是参与大多数持续性感染，仍有很多要了解的决定因素的细菌耐清除内生物膜。建议的工作的完成将提高我们的生物膜的作用在中耳炎的临床背景下的理解。 公共卫生相关性：中耳炎是全球范围内常见且昂贵的儿科疾病，每年造成数十亿美元的总经济影响。中耳炎感染是儿科门诊就诊、新抗生素处方和鼓室引流管手术滴注的主要原因，以缓解慢性和复发性中耳炎是美国最常见的外科手术。流感病毒形成生物膜，这是持续感染的重要决定因素。本申请的重点是了解这些生物膜群落如何促进细菌在体内的持久性。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 application is for competitive renewal of an R01 project focused on defining determinants of bacterial persistence in biofilms during otitis media infections. Otitis media is caused by airway opportunists such as Haemophilus influenzae (Hi, which forms biofilm communities that promote bacterial persistence within the middle-ear chamber. During the first four years of support we have defined mechanism(s) involved in biofilm formation by Hi, and proved that biofilms promote bacterial persistence in vivo. For the next project period we will define determinants of biofilm resistance to host clearance. We hypothesize that biofilms promote bacterial resistance to clearance because of activation of bacterial stress-responses within the biofilm, and inherent resistance to host phagocytes. In order to address these hypotheses we will complete the following Specific Aims: Specific Aim 1: To delineate role(s) of bacterial stress-responses in Hi persistence during experimental otitis media. Specific Aim 2: To define resistance of Hi biofilms to phagocytic and extracellular killing. Although it is clear that the biofilm mode of growth is involved in the majority of persistent infections, much remains to be learned about the determinants of bacterial resistance to clearance within biofilms. The completion of the proposed work will enhance our understanding of the role of biofilms within the clinical context of otitis media. 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 has long been recognized as the most common bacterial causes of otitis media, and it is now clear that H. influenzae forms biofilms that are important determinants of persistent infections. The focus of this application is to understand how these biofilm communities promote 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.