UC Santa Cruz

The aims of my dissertation research were to characterize the activity of inhibitors targeting the bacterial virulence factor, the type III secretion system (T3SS). The T3SS is a needle-like apparatus used by dozens of bacterial pathogens to directly deposit bacterial effector toxins inside the cytoplasm of target host cells. This virulence factor is typically essential for bacterial survival and replication within the host, and dozens of T3SS- positive pathogens are the causative agents of relevant health threats. Importantly, these T3SSs are highly conserved between bacterial species that possess them, making them an attractive potential drug target.

The first half of this work focuses on taking advantage of the tightly regulated, processional assembly and deployment of the T3SS and designing and optimizing assays we can use to probe for inhibitory activity at discreet stages throughout this process.

The second goal of my dissertation research was to employ this assay to characterize an inhibitor of the T3SS, piericidin A1, and have determined the molecule inhibits T3SS needle assembly.