Poster Presentation BACPATH 2022

Exploring the potential of bacteriophages in treating multidrug-resistant Burkholderia cenocepacia complex (Bcc) lung infections in individuals with cystic fibrosis (CF) (#171)

Kak Ming Ling 1 , Jack S. Canning 1 , Renee N. Ng 1 2 , Stephen M. Stick 1 3 4 5 6 , Anthony Kicic 1 4 5 6 7 , AREST CF 1 5 8 9 , WAERP Program 1 10
  1. Wal-yan Respiratory Centre, Telethon Kids Institute, Nedlands, WESTERN AUSTRALIA, Australia
  2. School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia
  3. Division of Paediatrics, Medical School, The University of Western Australia, Nedlands, Western Australia, Australia
  4. 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, Western Australia, Australia
  5. Department of Respiratory and Sleep Medicine, Perth Children’s Hospital, Perth, Western Australia, Australia
  6. Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia
  7. School of Population Health, Curtin University, Perth, Western Australia, Australia
  8. Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  9. Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia
  10. St John of God Hospital, Subiaco, Western Australia, Australia

Chronic bacterial infections are the main cause of lung function decline in people with CF. Bcc are a complex of gram-negative bacteria that is particularly problematic due to their intrinsic resistance to antibiotics, making subsequent treatment particularly challenging. Infection in those with CF causes severe clinical deterioration associated with respiratory failure and lung function decline. Infection with Bcc can also progress to life-threatening complications such as cepacia syndrome and fulminant necrotising pneumonia with fatal outcomes. The lack of a standard, effective therapeutic regimen (triple antibiotic combination) to treat Bcc infection jeopardises the ability to improve the quality of life for these individuals. This study assessed the potential of bacteriophages (‘phages’) as an alternative therapy to treat chronic Bcc infections. Here, we isolated, characterised and determined the host range of phages specific to Bcc and selected phages assessed for therapeutic potential. Wastewater was initially filtered through 0.22µm filters to remove the presence of microorganisms. Filtrates were used for direct phage isolation and enrichment methods. Host range activities of phages against 20 CF-derived Bcc species were demonstrated using a miniaturised spot-on assay. Bactericidal activity was assessed by measuring optical density at 600nm at desired temperatures (37℃ and 30℃) and durations (hourly). From 3 environmental wastewater collections, we have successfully isolated 38 stable phages that showed lytic activity against 14 CF-derived clinical isolates (i.e., B. cenocepacia, B. arboris, B. vietnamiensis, B. multivorans and B. cepacia). The top 20 phages with the broadest host range have been selected for genomic sequencing and bioinformatic analysis. In addition, the safety and efficacy of phages on Bcc infection will be determined via in vitro primary airway epithelial cells. Outcomes from this pipeline will benefit those with CF who have Bcc infections, providing supporting evidence for clinical translation.