With the increase of
infections due to multidrug resistant bacterial pathogens and the shortage of antimicrobial molecules with novel targets, interest in bacteriophages as a therapeutic option has regained much attraction. Before the launch of future clinical trials, in vitro studies are required to better evaluate the efficacies and potential pitfalls of such
therapies. Here we studied in an ex vivo human airway epithelial cell line model the efficacy of phage and
ciprofloxacin alone and in combination to treat
infection by Pseudomonas aeruginosa. The Calu-3 cell line and the isogenic CFTR knock down cell line (cftr-) infected apically with P. aeruginosa strain PAO1 showed a progressive reduction in transepithelial resistance during 24 h. Administration at 6 h p.i. of single phage, phage cocktails or
ciprofloxacin alone prevented epithelial layer destruction at 24 h p.i. Bacterial regrowth, due to phage resistant mutants harboring mutations in LPS synthesis genes, occurred thereafter both in vitro and ex vivo. However, co-administration of two phages combined with
ciprofloxacin efficiently prevented PAO1 regrowth and maintained epithelial cell integrity at 72 p.i. The phage/
ciprofloxacin treatment did not induce an inflammatory response in the tested cell lines as determined by nanoString® gene expression analysis. We conclude that combination of phage and
ciprofloxacin efficiently protects wild type and cftr- epithelial cells from
infection by P. aeruginosa and emergence of phage resistant mutants without inducing an inflammatory response. Hence, phage-
antibiotic combination should be a safe and promising anti-Pseudomonas
therapy for future clinical trials potentially including
cystic fibrosis patients.