Targeting M. catarrhalis for Prevention and Treatment of Otitis Media

 描述(申请人提供)：卡他莫拉氏菌是一种革兰氏阴性细菌粘膜病原体，是婴儿和儿童中耳感染(中耳炎(OM))和鼻窦炎的重要原因，也是成人肺部疾病恶化的重要来源。大约80%的3岁以下儿童至少会经历一次OM发作，许多儿童会经历反复发作的疾病，这可能会导致听力障碍和发育/学习问题。OM是直接和间接保健费用的一个重要来源，卡特哈里分枝杆菌每年有300万至400万儿科医生就诊。慢性或复发性OM现在被认为是一种生物膜病，已有大量报告表明卡他毛虫在体内形成生物膜。宿主表面的生物膜促进粘膜组织的粘附性和持久性，提供对宿主防御和抗生素的保护，是慢性疾病的主要来源。重要的是，多项研究表明，卡他分支杆菌在鼻咽部的定植促进了另外两种主要耳科致病菌肺炎链球菌和/或非分型流感嗜血杆菌(NTHI)的持续定植，从而显著增加了OM的风险。这项拟议的研究项目的第一个目标是彻底了解卡他毛杆菌对其他耳部病原体稳定和持久定植的贡献，从而促进OM的发展。此外，旨在根除中耳浮游和生物膜相关细菌的新的治疗方法不仅将显著减少幼儿持续使用抗生素，还将减少相关的发病率和进行鼓室造口管插入手术的需要。因此，这项研究计划的第二个目标是将光动力疗法(PDT)转变为一种有效的、非侵入性的治疗方法，用于治疗由卡他单胞菌和多菌生物膜引起的急性和慢性OM。

 DESCRIPTION (provided by applicant): Moraxella catarrhalis, a Gram-negative bacterial mucosal pathogen, is a significant cause of middle ear infections (otitis media (OM)) and sinusitis in infants and children and an important source of exacerbations in adults with lung disease. Approximately 80% of all children under 3 will experience at least one episode of OM and many experience recurrent disease, which may result in hearing impairment and developmental/learning problems. OM is a significant source of direct and indirect health care costs and M. catarrhalis is responsible for 3 to 4 million pediatrician office visits annually. Chronic or recurrent OM is now considered a biofilm disease and there have been numerous reports demonstrating that M. catarrhalis forms biofilms in vivo. Biofilms on host surfaces promote adherence and persistence on mucosal tissues, provide protection from host defenses and antibiotics, and represent a primary source of chronic disease. Importantly, multiple studies have suggested that nasopharyngeal colonization with M. catarrhalis promotes subsequent persistent colonization with the two other major otopathogens Streptococcus pneumoniae and/or nontypeable Haemophilus influenzae (NTHI), resulting in a significantly increased risk of OM. The first goal of this proposed research project is to provide a thorough understanding of the contribution of M. catarrhalis to the stable and persistent colonization of the other otopathogens, which then potentiates the development of OM. Moreover, novel therapeutic approaches designed to eradicate planktonic and biofilm-associated bacteria from the middle ear would not only significantly decrease the constant use of antibiotics in young children, it would also decrease the associated morbidity and the need to perform surgeries for insertion of tympanostomy tubes. Thus, the second goal of this research plan is to adapt photodynamic therapy (PDT) into an efficacious, noninvasive treatment for both acute and chronic OM resulting from M. catarrhalis monospecies and polymicrobial biofilms.