Phages-antibiotics combinations against biofilms in the context of cystic fibrosis

Details

Supervisors

Van Bambeke, Françoise

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences biomédicales, à finalité approfondie

Abstract

enCystic fibrosis is a hereditary genetic disorder caused by a mutation in the CFTR gene leading to an accumulation of thick and sticky mucus in the lungs that render immune cells and antibiotics less efficient, resulting in many bacterial infections. The two main co-isolated pathogens from patients with cystic fibrosis are Staphylococcus aureus and Pseudomonas aeruginosa. They have the ability to survive in the lungs by forming biofilms which favor the emergence of resistant or tolerant bacteria and therefore making it hard to treat those infections. Bacteriophages offer a potential adjunct strategy to conventional antibiotics for managing biofilm-related infections. That is why the objective of the project is to evaluate the potential synergy of a phage-antibiotic combination on biofilms formed with clinical strains of either Staphylococcus aureus or Pseudomonas aeruginosa, co-isolated from the same patients with cystic fibrosis. Firstly, in order to know when biofilms’ growth becomes stable, CFU’s counting and crystal violet staining were performed on the biofilms let to grow for either 24, 48, 72 or 96 hours in ASM+ medium (a medium mimicking the mucus of patients with cystic fibrosis). Results have shown that the strains have stable CFU and biomass after either 48 hours or 72 hours, meaning that biofilm’s growth stabilized after 72 hours. Knowing that, a screening of the phages-antibiotics combinations was performed on Staphylococcus aureus strains assessing the biomass of biofilms let to grow for 72 hours then treated with the chosen phage-antibiotic combinations. From this screening, five synergistic combinations emerged. Mature biofilms were then treated with those five combinations to assess the CFU count with a goal of confirming the synergistic effect of the combinations. Out of the five combinations, only one displayed a synergistic effect on the CFU’s counting confirmed by its bliss score. Overall, this work demonstrated that phage-antibiotic synergy against staphylococcal biofilms is highly dependent on strain and dosing parameters, supporting personalized approaches and kinetic screening for clinical translation.