01.
the brief
Antimicrobial resistance (AMR) is one of the biggest threats facing healthcare and is projected to kill more people by 2050 than cancer, say experts. Patients with cystic fibrosis also may suffer from lung infections caused by multidrug-resistant bacteria, mainly Pseudomonas aeruginosa, Achromobacter xylosoxidans and Staphylococcus aureus. If antibiotics are no further option to treat these infections, bacteriophages might be an alternative. Bacteriophages, phages in brief, are viruses that can kill specific bacteria and that can be used therapeutically to cure patients infected with pathogenic bacteria. When a patient requests for phage therapy, the bacterial strains that is infecting them is tested against a set of different phages in the lab using a phagogram. Such a phagogram bring together bacteria and a phage to see if the phage is able to kill the bacterium. This phagogram is a rather simple in vitro model, not representing the complex in vivo lung situation.
02.
our goals
We aim to improve the way phages are selected for phage therapy in patients with cystic fibrosis. To do so, we will test different models with increasing complexity. We aim to test phagograms under anaerobic conditions, using a new platform named PMD4U, in biofilm models and in a 3D-lung-cell-biofilm model.
Second, we aim to characterize the lung bacterial and fungal microbiome of patients with cystic fibrosis.
03.
our approach
At the Ghent University Hospital, patients with cystic fibrosis will be followed longitudinally. Sputa will be cultured for the presence of Achromobacter xylosoxidans, Pseudomonas aeruginosa and Staphylococcus aereus. Cultured pathogens will be tested against our phage library, first using conventional phagograms.
Next, phagogram testing will be performed under anaerobic conditions, using a new platform developed by partner HOGENT named phage-measuring-device for you, PMD4U. PMD4U is revolutionary in that way that it measures interactions between phages and bacteria in real-time. In a next phage, we will test phages against pathogens grown in biofilms. In a last phase, lung cells will be grown in a 3D model, that will be used to grown pathogenic biofilms on. This model will be used to test our library of phages.
Sputa will be used to extra DNA and profile the bacterial and fungal microbiome making use of the Oxford Nanopore Technology next-generation sequencing technique.