Host defence peptide as an innovative novel therapy for Pseudomonas aeruginosa biofilm infections in the cystic fibrosis lung

Introduction/Aim
Pseudomonas aeruginosa biofilm colonization is associated with declining lung function in cystic fibrosis (CF) patients. Biofilm formation is typically resistant to antibiotics and no effective therapy has been developed yet for their treatment. Interest in host defence peptides (HDPs) has grown due to their potential therapeutic applications and their possible use against biofilm. Here, novel short, synthetic cationic peptides were tested for their anti-biofilm effectiveness as well as their ability to inhibit and disperse P. aeruginosa biofilms.

Method
Clinical isolates (n=30) of P. aeruginosa from CF patients were used to screen and evaluate a 17 novel anti-biofilm peptide candidate's activity (MIC/MBEC) in a high-throughput plate-based procedure, followed by confocal microscopy using live/dead bacteria staining. Their ability to inhibit and disperse the bacterial biofilms in human primary airway epithelial cell cultures derived from the CF children were assessed using an air-liquid interface (ALI) cell culture biofilm model and GFP tag bacteria.

Results
Six (HDP- 25,26,43,101,102,103) candidates were was found to exhibit anti-microbial, anti-attachment and anti-biofilm activity at 8-16 μg/mL compared with current conventional antibiotics (Amikacin 128-512 μg/mL/ Tobramycin 128-1024 μg/mL/ Ciprofloxacin 128-512 μg/mL). Of these, HDP 25, 26 and 102 were the most potent, resulting in >97% bio-volume reduction followed by induced disruption of the mature biofilms (ALI cultures), significant colony death (88-94%), 71% reduction in the production of the key chronic virulent factor pyocyanin, and 74% reduction of bacterial attachment to airway epithelial cells.

Conclusion
These findings highlight the potential of novel peptides as a new group of antimicrobial weapons for target and breaking down the biofilms associated with airway epithelium.