1. Exploring Phage-Antibiotic Synergies in The Context of Biofilm-related Infectious Diseases
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Dr Steven De Soir, MSc Hortence Parée, Dr. Nur Hidayatul Nazirah Kumarudin, Dr. Jeroen Waegemans, Professor Rob Lavigne, Professor Annabel Braem, Dr. Maya Merabishvilli, Dr. Daniel De Vos, Dr. Jean-Paul Pirnay, and Professor Françoise Van Bambeke
- Subjects
Infectious and parasitic diseases ,RC109-216 - Abstract
Introduction: Not only the emergence of resistance mechanisms towards routinely used antibiotics but also the formation of so-called biofilms, present in about 80% of clinical infections, is causing huge problems in the clinics. These (poly)microbial micro-communities are known to be much more resistant than their planktonic counterparts due to a metabolic shift. Bacteriophages, or phages in short, present an attractive alternative to try and eradicate these biofilms due to their potential enzymatic effect on biofilm matrix components especially when used in combination with antibiotics. Methods: more then 80 phage clones were isolated, purified and characterized from a wide variety of environmental sources (hospital sewages, lakes, etc). These phages, targeting both Pseudomonas aeruginosa & Staphylococcus aureus/epidermidis were administered with or without the presence of routinely used antibiotics (ciprofloxacin, meropenem, ceftazidime & tobramycin) on mono- and multispecies biofilm models in the context of infectious diseases. Biomass evaluations, cultivable cell counts, metabolic assays along with Scanning Electron Microscopy (SEM) were used to evaluate the dual treatment modality for its’ biofilm eradicating potential. Results & Discussion: Phage-antibiotic synergy assays on mono-species biofilms repeatedly indicated highest biofilm disruption with the combined treatment modality, while maximum reductions were seen on mono-species biofilms formed by P. aeruginosa when combining phage PSP3 (a Pbunavirus) with ceftazidime, resulting in 4.52log10 decrease in cultivable cells. When P. aeruginosa biofilms were grown on titanium coupons, mimicking orthopedic implant material, highest biofilm removal was observed when combining phage PSP30 (Bruynoghevirus) with ciprofloxacin, rather then using any sequential therapy.When performing phage-antibiotic synergy assays on dual-species biofilms including both beforementioned bacterial species and grown in Artificial Sputum Media (ASM), mimicking mucus found in Cystic Fibrosis (CF) patients, highest biofilm removal was observed when using the combined treatment approach (phage PSP3, targeting P. aeruginosa, and phage ISP, targeting S. aureus). Biomass reductions of up to 90% were observed with significant potentiation of the antibiotic effect when co-administered with the phage cocktail. Although for P. aeruginosa, reductions in CFU counts were seen to be improved when adding the phage cocktail to antibiotics, S. aureus populations were seen to be much less affected. Conclusion: the combined use of phages and routinely used antibiotics for the treatment of biofilm-related infections is proven to be much more effective compared to any monotherapy thereby providing a promising treatment approach for biofilm-related infectious diseases.
- Published
- 2025
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