Bacterial biofilms in otitis media

描述(由申请人提供)：此申请是R01项目的竞争性续签，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。中耳炎是由呼吸道机会主义者引起的，如流感嗜血杆菌(Hi)，它形成的生物膜群落促进细菌在中耳室内的持久性。在支持的最初四年中，我们确定了Hi参与生物膜形成的机制(S)，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，我们将确定生物膜抵抗宿主清除的决定因素。我们假设，生物膜促进了细菌对清除的抵抗力，因为生物膜内的细菌应激反应被激活，以及对宿主吞噬细胞的固有抵抗力。为了解决这些假说，我们将完成以下具体目标：具体目标1：描述细菌应激反应在实验性中耳炎高持续性中的作用(S)。特定目的2：确定Hi生物膜对吞噬细胞和细胞外杀伤的抵抗力。虽然很明显，生物膜的生长模式与大多数持续性感染有关，但关于细菌对生物膜内清除的抵抗力的决定因素，仍有许多需要了解。拟议工作的完成将增强我们对生物膜在中耳炎临床背景下的作用的理解。

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.