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This work addresses genetic and biochemical deficiencies revealed following the discovery of the polysaccharide synthesis locus (psl) and the psl-dependent polysaccharide required for biofilm formation in Pseudomonas aeruginosa .

We show that eleven of fifteen psl genes are required for Psl production and surface attachment in the nonmucoid strain PAO1.

Structural analysis of Psl revealed a pentasaccharide repeating unit composed of mannose, rhamnose and glucose distinct from known polysaccharides produced by PAO1.

We examined enzymes involved in production of Psl precursors and found overlap with LPS sugar nucleotide biosynthetic pathways for all three sugars that comprise Psl.

In order to evaluate Psl and other in vitro biofilm mediators in vivo we developed a chinchilla otitis media model for P. aeruginosa. We found that P. aeruginosa readily forms biofilms in middle ears of chinchillas profoundly different from in vitro biofilms due to extensive involvement of host factors.

Certain biofilm mediators important in vitro, such as cyclic-di-GMP, increase persistence in vivo possibly as a result of greater Psl production.

Other systems that positively regulate virulence factor production, like the LasRI and RhlRI quorum sensing circuits, are detrimental to bacterial persistence and chinchilla survival.

Flagella, which are important inflammatory mediators, do not impact the course of infection in chinchillas.

In more focused in vitro work with psl-host interactions, we show that a psl mutant activates human PMNs to a greater degree than does PAO1, but without affecting PMN killing of P. aeruginosa. We also show that Psl, likely through its role as an adhesin, increases flagellin-dependent activation of the proinflammatory transcription factor NF-kappaB in human airway epithelial cells.

The added knowledge of Psl presented in this work lays the groundwork for future studies of individual Psl proteins and how Psl structure contributes to adhesion.

We show that the chinchilla model can be used to study P. aeruginosa infections and adds significantly to knowledge of biofilm and virulence determinants in vivo.

Future studies based on this research will continue to define the molecular mechanisms for Psl interactions with host tissues and seek to understand the evolutionary advantage of Psl expression during an infection.

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Product Details
1243771097 / 9781243771094
Paperback / softback
01/09/2011
United States
34 pages, black & white illustrations
189 x 246 mm, 82 grams
General (US: Trade) Learn More