RAPID-PHAGE: Implementing a screening tool to rapidly match bacteriophages for resistant bacteria in people with Cystic Fibrosis

Project Duration – 1 Year

Associate Professor Anthony Kicic and his team from Curtin University in Western Australia are working on a way to quickly and accurately identify bacteriophages (phages) that can treat bacterial lung infections in people with Cystic Fibrosis (CF).

The Phage WA research program has been developed over several years and the team has been able to build a large phage biobank of more than 3,500 phages, available to treat multiple bacterial infections including Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus) Burkholderia cenocepacia (B. cenocepacia), and Acinetobacter baumannii (A. baumannii).  The team has also tested their phages in pre-clinical models and will be able to provide phage therapy for people with CF on compassionate grounds. The next step is to find a rapid and accurate process to match the right phage to combat each specific bacterial infection.

With Cure4CF funding, Associate Professor Kicic’s team will:

1. Screen adults and children with CF who have bacterial infections that are resistant to antibiotics and characterise the isolates.
2. Test an Artificial Intelligence (AI) phage-matching tool against regular phage-matching processes to determine the tool’s accuracy and efficiency.

Why use bacteriophages?

Bacteriophages (phages) are specific and specialised viruses that kill bacteria without harming human cells. They are the bacteria’s natural predator. Unlike antibiotics, phages are highly specific and attack only the targeted bacterial strain, without harming beneficial microbiota or the person themselves. To be used as a treatment, phages need to be identified and then matched against a patient’s bacterial isolate. Traditionally this process requires days of laboratory testing which is labour and time-intensive. 

To find a phage match, researchers need to know a lot of information about the specific bacteria that is causing problems for the patient. This is done by isolating the genes from the bacteria and characterising them carefully.  This genetic code is then used to match up with a phage from a library and if one does not exist, they may have to source new phages. 

The team in Perth has a very large existing library of phages to target many common respiratory pathogens.  Importantly, some of the phages can target many strains of the same bacteria, which means they may be able to be used for many patients.  Each phage has undergone a careful assessment of their genetic code and other tests to ensure they can kill the bacteria without harming lung cells in the process.  

Why use an AI phage matching tool?

Because traditional phage matching can take a long time (days or weeks), the team has developed an artificial intelligence (AI) tool that aims to match a phage within a day of identifying the target bacteria.  To know if the AI tool is as good as or better than traditional manual laboratory phage matching, they need to compare how the two approaches work. They will test the ability of their AI tool against traditional manual screening processes to determine how long each matching method takes and how well the phage matches the bacteria. Their goal is to determine if using AI phage matching can help clinicians deliver the most safe and effective treatment in the shortest time possible. 

How can this project help bacteriophage therapy reach the clinic?

The team plans to translate their phage bank, screening processes, and AI matching tool into a clinical phage therapeutic pipeline. The team has already established a dedicated facility for the manufacture of highly pure pharmaceutical-grade phage products produced at a good manufacturing practice level (the standards to which all medicines are manufactured). Using this facility to prepare phages, the team hopes to be able to provide a phage matching service for people with CF across Australia. With a comprehensive phage matching and manufacturing pipeline, the team will be then ready to provide personalised phage therapy for individuals in need, as well as manufacture phage products for traditional clinical trials.

The Cure4CF Project is an essential step in this process to provide targeted and personalised treatment.  By reducing the time needed for phage matching, patients can receive timely care, leading to quicker recovery and less time spent in hospital.

About Associate Professor Kicic

Associate Professor Kicic completed his undergraduate and doctorate degrees at the University of Western Australia, specializing in Molecular Biology and Cell Biology. His research interests lie in tissue engineering and reparative cell biology, particularly focusing on the ability of the cells in the body to repair, including stem cells. Qualified in these areas, he has previously been responsible founding a Stem Cell Unit (Lions Eye Institute, Perth), establishing dedicated laboratories for stem cell research and establishing stem cell isolation and differentiation techniques for both embryonic and adult-derived stem cells.

Associate Professor Kicic is currently the Rothwell Family Fellow; Head, Airway Epithelial Research at The Kids Research Institute and began working with phages and their potential to treat lung infections in 2016.  Since this time, he has led the WA phage research and translation pipeline, including establishing the largest phage library, with over 2000 phages specific to several types of bacteria including P. aeruginosa, S. aureus, B. cenocepacia, and A. baumannii.