Using bacteriophages and antibiotics in combination to control pathogenic bacteria

Multidrug resistance (MDR) is becoming an increasing threat to the global public health and Pseudomonas aeruginosa is one of the leading causes of nosocomial infections as it can quickly develop resistance to clinical antibiotics. The rise of MDR has rejuvenated interest in alternative therapies where, for example, pathogen-specific phages could be used on their own or alongside antibiotics to improve treatment efficacy. Benefits of phages include high pathogen specificity, efficacy against antibiotic-resistant bacterial genotypes and their ability to co-evolve to overcome evolution of phage resistance. Phages also have low toxicity to the patients, minimal disruption of the patient’s microbiota, and can auto- “dose” themselves by replicating in their host pathogens. This research investigates using phages and antibiotics in combination therapy in vitro against the Pseudomonas aeruginosa bacterial pathogen. The main aim was to identify effective phage-antibiotic combinations using various commonly used clinical antibiotics and LPS and pilus-targeting phages that have been shown to be effective against P. aeruginosa previously. Results show that certain combinations of antibiotics and bacteriophages are more efficient at suppressing bacterial growth than the others. Specifically, it was found that antibiotic combinations retain their synergies, antagonistic or not, even when phages are added. Furthermore, we show that two bacteriophages alongside one antibiotic is likely to be the best combination for designing efficient phage-antibiotic therapy cocktails. Interestingly, antibiotic-phage synergies were different when applied against clinical P. aeruginosa strains. Together, these results suggest further research on combination therapies aimed to suppress bacterial growth is needed, and specifically, combinations therapies need to be tested not only against laboratory but also against clinical strains to obtain effective outcomes.