Moraxella (Branhamella) catarrhalis is now acknowledged to be an important cause of otitis media in infants and young children and can also cause lower respiratory tract infections in adults with chronic obstructive pulmonary disease. Little is known about the gene products that allow M. catarrhalis to colonize the nasopharynx and then cause disease in the respiratory tract. However, the ability to attach to human cells and to resist killing by normal human serum (i.e., serum resistance) are well-recognized bacterial virulence factors. We have identified two different proteins (UspA1 and UspA2) that are exposed on the surface of this pathogen and that perform distinct functions relevant to the ability of M. catarrhalis to colonize and survive in vivo. We already have established that UspA1 is an adhesin that binds human epithelial cells in vitro. We also have proven that UspA2 is directly involved in the expression of serum resistance by this organism. This research project involves investigation of the structure-function relationships inherent in these two proteins and also addresses two other topics that are relevant to the infectious process involving M. catarrhalis. In the first Specific Aim, we will identify the amino acid sequence(s) in the UspA1 protein that allows it to bind human epithelial cells. In the second Specific Aim, we will identify both the mechanism by which UspA2 confers serum resistance on M. catarrhalis and the amino acid sequence(s) in UspA2 responsible for this activity. Experiments designed to determine the level of UspA2 required for serum resistance and how UspA2 expression is regulated constitute the third Specific Aim. Finally, we will investigate biofilm formation by M. catarrhalis and identify gene products involved in this biologically relevant process in the fourth Specific Aim.
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