Developing synthetic targets to identify the receptor for Bordetella filamentous hemagglutinin

Bordetella is a respiratory pathogen that uses a variety of protein adhesins to colonize the mammalian respiratory epithelia. The gene encoding Filamentous Hemagglutinin (FhaB) is required for colonization of the respiratory tract. Recent work in our lab has identified the receptor-binding domain on FhaB that is responsible for adhesion to mammalian cells. Despite FhaB’s importance in disease, its cognate receptor on the host cell has not been identified. The major goal of my project is to identify eukaryotic lipids that interact with the FhaB-RBD. To do this, I constructed synthetic target cells, consisting of a defined lipid bilayer on a silica bead, and tested whether candidate lipid receptors support FhaB-RBD-mediated binding. I have found that polar lipids extracted from porcine brain cells support FhaB-RBD-dependent binding, supporting the hypothesis that the FhaB receptor is a mammalian lipid.