JENNINGS LAB
Biofilm Polysaccharides
Influence of bacterial polysaccharides on therapeutic outcomes
Fig. 1. Pel and Psl extracellular polysaccharides are expressed in cystic fibrosis sputum, where they bind extracellular DNA (eDNA) and impede antibiotic and mucolytic treatments.
Funding:
American Heart Association Postdoctoral Fellowship
Summary
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Pel is an extracellular polysaccharide that is important for the formation of bacterial aggregates called biofilms. Despite Pel's importance in biofilm formation, its structure and mechanism of adhesion was not known. We showed that Pel is a cationic, amino sugar polymer. The cationic charge is important for its function in biofilms, allowing it to bind extracellular DNA via an ionic binding mechanism (Jennings PNAS).
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How bacterial aggregates form in the cystic fibrosis airways is controversial and unclear. Using immunohistochemistry, we provide direct evidence that Pel and Psl exopolysaccharides are produced by P. aeruginosa aggregates in cystic fibrosis sputum, and aggregate morphology is consistent with a polysaccharide-dependent aggregation mechanism (Jennings Cell Reports).
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Extracellular DNA (eDNA) is abundant in the cystic fibrosis airways. We reasoned that Pel's ability to bind eDNA may interfere with antibiotics and mucolytic drugs aimed at thinning the airway mucus by digesting DNA. We found that Pel-eDNA interactions increased antimicrobial tolerance to tobramycin and protected DNA from DNase digestion (Jennings Cell Reports). The findings suggest Pel likely diminishes the efficacy of two common cystic fibrosis therapeutics.
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Impact: Collectively this work provides insight into the biological function of bacterial exopolysaccharides in vivo. Moreover, it highlights the potential use of Pel as an important antibacterial target. ​​