Certain strains of P. aeruginosa bacteria secrete alginate, an exopolysaccharide that forms a viscous coating around the bacteria, and helps protect it from the host immune response during infection. The alginate coating is also believed to diminish the effectiveness of many antibiotics against P. aeruginosa . Because of alginate's role in CF pathogenesis, enzymes responsible for the biosynthesis of alginate in P. aeruginosa are attractive candidates for inhibitor design. Originally identified by genetic and microbiological studies, preliminary characterizations of these enzymes have been published, but detailed mechanistic studies have not been performed. This information is critical to understanding the mechanism of action of these enzymes and for future efforts at inhibitor design.
Structure determination is in progress.
Opportunities exist to crystallize other enzymes in the pathway as they become available. In addition, high-resolution studies of PMM and GMD with substrate analogs and inhibitors will also soon be available.