| Talk title | Structure-guided disruption of pseudopilus protein complex inhibits Type II secretion system in Pseudomonas aeruginosa |
| Speaker | Prof. Zongchao JIA Professor, Department of Biomedical and Molecular Sciences, Queen’s University, Canada |
| Date & Time | 9 May 2017 (Tuesday) 15:00-16:00 |
| Venue | Room G004, E12 Building (University of Macau) |
| Abstract | Pseudomonas aeruginosa is classified by WHO to be one of the human pathogens which most urgently needs antibiotics in the category of “Priority 1: critical”. This infectious bacterium utilizes the Type II secretion system to translocate virulence factors through the periplasm into the extracellular environment. In T2SS, five pseudopilins assemble a piston-like pseudopilus that pushes secretion substrates out of the cell. We show that the two minor pseudopilins, XcpV and XcpW, constitute an indispensable core binary complex of the pseudopilus tip. Loss of XcpV and -W, instead of XcpU and -X, results in the inhibition of T2SS. We have determined the crystal structures of XcpVW binary and XcpVWX ternary core complexes and tested structure-based inhibitory peptides and compounds. The peptides not only disrupted the core XcpVW binary complex and the entire pseudopilus tip complex of XcpUVWX in vitro but also inhibited the Type II secretion of lipase in vivo. Inhibitory compounds, targeting the cavity closest to the interaction interface, were screened in silico and exhibited proof-in-principal T2SS inhibitory activity. |
