Diego Orellana

Examining the Sequence Determinants of FhaB Toxicity in Bordetella pertussis

Filamentous hemagglutinin (FHA) is a secreted protein that is important for the adhesion of Bordetella pertussis, the bacterium that causes whopping cough, to the respiratory epithelium of mammals. FhaB is a precursor protein whose C-terminus is cleaved to yield the mature FHA protein. Previous investigations suggest that the C-terminus of FhaB stabilizes FHA during secretion. However, based on sequence alignments to the conserved type six secretion systems of other bacteria, we hypothesize that FhaB C-terminal domain functions as a mammalian cell toxin. To further understand the role of the FhaB C-terminal domain in pathogenesis, I will use bioinformatics approaches to identify evolutionarily conserved sequence motifs and will assist in the design of mutagenesis studies to disrupt these motifs.  In doing so, we anticipate gaining new knowledge that could be used to guide biotechnological improvements to the FHA component of the whooping cough vaccine.