MORAXELLA CATARRHALIS OUTER MEMBRANE PROTEINS AND THEIR INTERACTIONS WITH THE HUMAN HOST

Abstract: Moraxella catarrhalis is an airway pathogen whose role in infection has been increasingly recognized in recent years. Most authorities in this field now agree that M. catarrhalis causes significant morbidity and is not just a harmless commensal. The universal prevalence of BRO ?-lactamases in this pathogen is a serious concern. In addition, M. catarrhalis may be further propelled into a more prominent position in the hierarchy of respiratory infectious agents due to the phenomenon of ?non-vaccine type replacement? as a result of the wider usage of vaccines against other pathogens in the same ecological niche, such as Haemophilus influenzae and Streptococcus pneumoniae. There is currently no available vaccine against M. catarrhalis. A detailed analysis of the interactions of this bacterium with the human host is necessary to identify ways to interfere with its colonization and infection. To this end, we have focused on the interactions via three outer membrane proteins, namely UspA1 (ubiquitous surface protein A1), UspA2 and MID (Moraxella catarrhalis IgD binding protein). We found that UspA1 and A2 could bind fibronectin and laminin, and characterized these interactions. We also detailed a novel interaction of UspA1 and A2 with the complement protein C3. The UspA1/A2-dependent C3 binding contributes to its serum resistant phenotype and is a way in which M. catarrhalis combat the innate immunity. Furthermore, we showed that this interaction could contribute to the survival of copathogens. An analysis of naturally acquired serological responses to these two proteins and those of MID showed that the functional domains identified here (fibronectin binding region in UspA1299-452 and UspA2165-318, C3 binding region in UspA2) and those identified in other studies (CEACAM binding region of UspA1, the MID764-913 adhesive domain) evoked significant immune responses. The better understanding of the interactions and the identification of important domains in these three proteins represent significant advances in the quest for a suitable vaccine against M. catarrhalis.