Mucin promotes Psl production and surface exploration in Pseudomonas aeruginosa

In chronic, recalcitrant infections, Pseudomonas aeruginosa forms biofilm aggregates that are encapsulated in a protective extracellular matrix made of exopolysaccharides, extracellular DNA, and matrix proteins. Biofilm formation is a major cause of antibiotic clearance failure in P. aeruginosa , and there is growing pressure to elucidate biofilm preventative measures and develop novel anti-biofilm treatments. Toward this goal, much work has been done to understand the genetic adaptations P. aeruginosa undergoes in chronic respiratory infections, but how the mucosal environment, found in the lung, impacts P. aeruginosa behavior is unclear. Mucus is a protective hydrogel lining wet epithelial cells and is mainly composed of water and its structural component, the glycoprotein mucin. Using commercially purified porcine gastric mucin, which is missing its end tail regions and has modified glycosylation, as a model of structurally altered mucus, we show that P. aeruginosa rapidly increases surface exploration via twitching motility, depositing trails of the exopolysaccharide Psl and elevating total Psl levels. This increased Psl production occurs on short timescales (<1 h), is independent of transcriptional or translational regulation, and enhances tolerance to select antimicrobials, including hydrogen peroxide and ciprofloxacin. Together, these findings indicate that structurally altered mucus environments function as contextual signals that elicit rapid, non-genetic bacterial adaptive behaviors relevant to persistence in chronic infection.