title: Antimicrobial efficacy against Pseudomonas aeruginosa biofilm formation in a three-dimensional lung epithelial model and the influence of fetal bovine serum.
abstract: 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.
authors.affiliation: Laboratory of Pharmaceutical Microbiology (LPM), Ghent University, Ghent, Belgium.|The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Crabbé
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Pharmaceutical Microbiology (LPM), Ghent University, Ghent, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Matthijs
authors.affiliation: Laboratory of Pharmaceutical Microbiology (LPM), Ghent University, Ghent, Belgium.
authors.forename: Petra
authors.initials: P
authors.lastname: Rigole
authors.affiliation: University of British Columbia, Centre for Microbial Diseases and Immunity Research, Vancouver, British Columbia, Canada.
authors.forename: César
authors.initials: C
authors.lastname: De La Fuente-Nùñez
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Davis
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Ledesma
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Shameema
authors.initials: S
authors.lastname: Sarker
authors.affiliation: Unit of Microbiology, Belgian Nuclear Research Centre (SCK·CEN), Mol, Belgium.
authors.forename: Rob
authors.initials: R
authors.lastname: Van Houdt
authors.affiliation: University of British Columbia, Centre for Microbial Diseases and Immunity Research, Vancouver, British Columbia, Canada.
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.affiliation: Laboratory of Pharmaceutical Microbiology (LPM), Ghent University, Ghent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Coenye
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.|School of Life Sciences, Arizona State University, Tempe, Arizona 85287, United States of America.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Nickerson
mesh_terms: D000072283:A549 Cells; D000583:Amikacin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002417:Cattle; D018929:Cell Culture Techniques; D003091:Colistin / Q000494:pharmacology; D004357:Drug Synergism; D005333:Fetus; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009842:Oligopeptides / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D044967:Serum / Q000737:chemistry*; D019108:Tight Junctions / Q000187:drug effects / Q000382:microbiology / Q000648:ultrastructure; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; C000602801:DJK-5 peptide; D005839:Gentamicins; D009842:Oligopeptides; D000583:Amikacin; D014031:Tobramycin; D003091:Colistin