Oral Presentation BACPATH 2019

A pipeline for bacteriophage (phage) discovery, characterization and pre-clinical evaluation. (#29)

Rhys Dunstan 1 , Rebecca Bamert 1 , Murray White 1 , Richard Strugnell 2 , Matthew Belousoff 3 , Trevor Lithgow 1
  1. Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, VIC, Australia
  2. Department of Microbiology & Immunology, University of Melbourne, Parkville
  3. Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia

The rise in resistance to existing antimicrobial drugs is a major global health threat. These antimicrobial resistant (AMR) infections are caused by bacteria and fungi of various species, collectively referred to as “superbugs”. Klebsiella is now established as a pathogen with high rates of AMR and concurrent mortality in humans, and work in our lab is directed towards reversing the evolution of AMR phenotypes in Klebsiella. Approaches to combat AMR that obviate the need for new drugs include the re-engineering/re-purposing of existing drugs, and phage therapy. Bacteriophage (phage) are viruses that selectively kill bacteria, and have proven effective in curing infections caused by superbugs. We have been working in two areas of importance in phage therapy: the discovery of diverse phage for use in producing “phage cocktails” for therapy, and detailed means for characterization of new phages towards adapting them as biologics. Using environmental water samples from around the world, we discovered phage with diverse tail structures targeting Klebsiella by diverse means. Cryo-electron microscopy is being used to understand the tail structures, and work towards developing biologics isolated from phages, including robust enzymes that degrade bacterial biofilms, are being pursued.