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In vitro  models that mimic  in vivo  host-pathogen interactions are needed to evaluate candidate drugs that inhibit bacterial virulence traits. We established a new approach to study  Pseudomonas aeruginosa  biofilm susceptibility on biotic surfaces, using a three-dimensional (3-D) lung epithelial cell model.  P. aeruginosa  formed antibiotic resistant biofilms on 3-D cells without affecting cell viability. The biofilm-inhibitory activity of antibiotics and/or the anti-biofilm peptide DJK-5 were evaluated on 3-D cells compared to a plastic surface, in medium with and without fetal bovine serum (FBS). In both media, aminoglycosides were more efficacious in the 3-D cell model. In serum-free medium, most antibiotics (except polymyxins) showed enhanced efficacy when 3-D cells were present. In medium with FBS, colistin was less efficacious in the 3-D cell model. DJK-5 exerted potent inhibition of  P. aeruginosa  association with both substrates, only in serum-free medium. DJK-5 showed stronger inhibitory activity against  P. aeruginosa  associated with plastic compared to 3-D cells. The combined addition of tobramycin and DJK-5 exhibited more potent ability to inhibit  P. aeruginosa  association with both substrates. In conclusion, lung epithelial cells influence the efficacy of most antimicrobials against  P. aeruginosa  biofilm formation, which in turn depends on the presence or absence of FBS.

scientific reports

Antimicrobial efficacy against Pseudomonas aeruginosa biofilm formation in a three-dimensional lung epithelial model and the influence of fetal bovine serum