Poster Presentation BACPATH 2019

Exploring the therapeutic potential of phage therapy to treat Pseudomonas aeruginosa infection in people with cystic fibrosis (#204)

Renee N Ng 1 2 , Andrew Vaitekenas 3 , Matthew WP Poh 2 , Scott G Winslow 2 , Daniel R Laucirica 2 , Jessica Hillas 2 , Stephanie Trend 2 4 , Barbara J Chang 5 , Stephen M Stick 2 4 6 7 , Anthony Kicic 2 4 6 7 8 , AREST CF 2 6 9 10 , WAERP 2 11
  1. School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia
  2. Telethon Kids Institute, Perth, WA, Australia
  3. School of Pharmacy and Biomedical Sciences, Curtin University, Perth, WA, Australia
  4. Division of Paediatrics, School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia
  5. The Marshall Centre for Infectious Diseases Research and Training, School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia
  6. Department of Respiratory Medicine, Perth Children’s Hospital, Perth, WA, Australia
  7. Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Perth, WA, Australia
  8. Occupation and the Environment, School of Public Health, Curtin University, Perth, WA, Australia
  9. Murdoch Children's Research Institute, Melbourne, VIC, Australia
  10. Department of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia
  11. St John of God Hospital, Subiaco, Perth, WA, Australia

Cystic fibrosis (CF), a genetic disease caused by mutations in the CFTR gene, leads to mucus build-up in the lungs of patients, creating an ideal environment for the growth of Pseudomonas aeruginosa (P. aeruginosa). Most CF patients will be persistently colonised by P. aeruginosa by the time they reach adulthood. P. aeruginosa infections are associated with a rapid decline in pulmonary lung function and increased risk of morbidity and mortality. Importantly, P. aeruginosa harnesses multiple intrinsic virulence factors that allows immune response evasion and resistance to antimicrobials. Chronic infection promotes further acquisition of resistance genes via adaptive mutations. In addition, P. aeruginosa forms biofilms which limits efficacy of antibiotic treatment. In this study, we seek to explore alternative treatments targeting P. aeruginosa infection in CF lungs, specifically using bacteriophages, or “phages” as a novel antimicrobial therapy. Over 75 environmental water samples were collected from freshwater ponds located around the Perth metropolitan area. Samples were filtered with 0.22µm filters to remove the presence of environmental microorganisms present within the ponds. Filtrates were then assessed by plaque assay for presence of P. aeruginosa specific phage using strain PA01 (ATCC 15692). Phage isolates exhibiting anti-P. aeruginosa activity were propagated from at least 4 water samples collected. These isolates were further characterized for their stability and lytic capabilities as well as their ability to clear P. aeruginosa in relevant infection models. Here, primary airway epithelial cells from children with CF will be cultured at air liquid interface to form a differentiated epithelial layer, then inoculated with biofilm forming P. aeruginosa and treated with phage. The effect of phage treatment will then be assessed by measuring bacterial load and epithelial inflammatory cytokine production. Generated results will give insights into the efficacy of phage therapy in CF with the potential to develop a novel therapeutic pipeline to help treat CF bacterial lung infections.