Fighting pseudomonas aeruginosa and nontypeable

PURPOSE: The community behavior of bacteria biofilm infections may contribute towards enhanced disease pathogenesis. The consequently high mortality/morbidity rates associated to community and hospital-acquired pneumonia, ventilator-associated pneumonia, chronic obstructive pulmonary disease, cystic fibrosis, asthma, and bronchitis in conjunction with the global crisis of antibiotic resistance has promoted the search for novel therapeutic strategies to fight biofilm infections in the lung.

METHODS: The action of 17 novel anti-biofilm peptide candidates were firstly evaluated against clinical isolates of P. aeruginosa and Nontypeable H. influenzae via a high-throughput plate-based assay, coupled with confocal microscopy using live/dead bacteria staining. The ability of candidate peptides to eliminate biofilm on human primary airway epithelial cell cultures derived from children with CF were assessed using an air-liquid interface (ALI) cell culture biofilm model together with GFP tag bacteria.

RESULTS: Six candidate peptides (HDP- 25,26,43,101,102,103) were active at eradicating P. aeruginosa and Nontypeable H. influenza biofilms at relatively low concentrations (16-128μg/ml). High doses of current conventional antibiotics (Amikacin, Tobramycin and Ciprofloxacin; (128-1024μg/ml)) were unable to eradicate these biofilms. HDP 102 was the most potent peptide, driving >90% bio-volume reduction in airway epithelial cells and a74% reduction of bacterial attachment to these cells.

CONCLUSIONS: These findings highlight the potential of host defence peptides as a novel option to treat chronic bacterial biofilm infections in lung.

CLINICAL IMPLICATIONS: Insights gained through this work may offer solutions for targeted approaches to treat bacterial biofilms and improve the outcome of patients with chronic lung infections.

Authors: DL Wannigama, Anthony Kicic, Cameron Hurst, PN Monk, RJ Storer, Tanittha Chatsuwan, Stephen Stick.

Published in Chest Journal in April 2019.