Bacterial biofilms in otitis media

描述（由申请人提供）：本申请是R01项目的竞争性更新，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。中耳炎是由流感嗜血杆菌（Hi）等气道机会菌引起的，它们形成生物膜群落，促进细菌在中耳腔内持续存在。在最初四年的支持中，我们已经确定了Hi形成生物膜的机制，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，我们将确定生物膜抵抗宿主清除的决定因素。我们假设生物膜促进细菌对清除的抗性是因为生物膜内细菌应激反应的激活，以及对宿主吞噬细胞的固有抗性。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。特异性目的2：确定Hi生物膜对吞噬细胞和细胞外杀伤的耐药性。虽然生物膜的生长模式显然与大多数持续性感染有关，但关于细菌对生物膜内清除的抗性的决定因素仍有待了解。这项工作的完成将增强我们对生物膜在中耳炎临床环境中的作用的理解。

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.