Pel polysaccharide

In addition to mucoid P. aeruginosa strains, strains with a wrinkly small colony morphology and increased biofilm forming capacity have been isolated from CF sputum. These strains have increased expression of the Psl and Pel polysaccharides, and suggest that all three exopolysaccharides, alginate, Psl and Pel, play important roles in the colonization and maintenance of CF lung infections. Pel and Psl are the predominant polysaccharides found in biofilm infections in other clinical and all environmental settings, where together or individually they act as adhesins to maintain biofilm structure. Pel is a cationic polymer composed of 1,4 linked N-acetylglucosamine and N-acetylgalactosamine. Pel has been shown to initiate and maintain cell-to-cell interactions, and provide resistance to aminoglycoside antibiotics.

At present, our understanding of the molecular processes used by the seven proteins encoded on the pelABCDEFG operon to produce Pel is relatively limited. Our studies have shown that PelA is a multi-domain protein with both de-N-acetylase and hydrolase activities, and that while Pel polymerization, like alginate, is regulated by c-di-GMP, the inner membrane protein PelD uses a degenerate GGDEF domain rather than a PilZ domain (left).

Current projects

Our current projects are focused on:

• Characterizing the role of the outer membrane lipoprotein PelC.
• Determining how the polymer is exported via the multi-domain protein PelB.
• Determining whether the proteins interact to form a multi-protein complex or complexes and characterizing these interactions.
• Developing PelA as a therapeutic for the prevention and degradation of Pel-dependent biofilms.
• Identifying small molecule modulators of PelA deacetylase activity.