Plant Pathogen Guides Cancer Research

The bacterium Pseudomonas syringae is infamous for the brown rot spots it leaves on apples, pears, and many other crops. Now, a team of U.S. and European researchers led by Robert Dudler of the University of Zurich, in Switzerland, report the mechanism behind this plant pathogen's virulence and propose that this mechanism could inform cancer drug development (Nature 2008, 452, 755). The bacterium produces a peptide virulence factor called syringolin A (shown) that facilitates infection by inhibiting the plant cell's proteasome. The proteasome is essential for regulating many cellular functions in both plant and human cells. A hydroxyl group on one of the proteasome's threonine residues does a Michael-type 1,4-addition to syringolin A's α,β-unsaturated carbonyl (shown in red), forming a covalent bond. Because the proteasome is a promising anticancer target and syringolin A has been shown to thwart ovarian and neuroblastoma cancer cells, the authors note that this novel mechanism could guide the design of new proteasome inhibitors.