Targeting M. catarrhalis for Prevention and Treatment of Otitis Media

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 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.