Glycoside hydrolases enhance antibiotic activity against Pseudomonas aeruginosa biofilms from cystic fibrosis airways
Abstract
Pseudomonas aeruginosa forms antibiotic-tolerant biofilms in cystic fibrosis (CF) lungs. Targeting exopolysaccharides such as Psl and Pel offers a potential strategy to disrupt biofilms and improve antibiotic efficacy. Fourteen clinical CF P. aeruginosa isolates were screened for Psl- and Pel-dependent biofilm formation using crystal violet assays. The adjunctive effects of glycoside hydrolases (GHs) PslGh and PelAh with colistin, levofloxacin, and tobramycin (at peak sputum concentrations following nebulization) were evaluated using a high-throughput assay. Confocal microscopy visualized effects in live biofilms at subinhibitory antibiotic levels for two representative strains. Enzyme stability in CF sputum supernatant at 37°C was assessed via Western blot. Nine of 14 isolates showed PslGh-mediated disruption; only 3/14 were disrupted by PelAh. PslGh significantly enhanced antibiotic effects in 24 of 42 strain-antibiotic pairs (57%), compared with 5 of 42 (12%) for PelAh. Adjunctive effects were most pronounced with tobramycin, yielding 18.1% biofilm reduction. Confocal imaging confirmed additive effects when the GH corresponded to the exopolysaccharide to which the isolate had demonstrated disruption in the screening assay, but showed no benefit when targeting the other exopolysaccharide, even at higher enzyme doses. PslGh was more stable than PelAh in sputum, with PelAh degraded significantly by 4 and 20 h. GHs targeting exopolysaccharides associated with biofilm…
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