Exploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivo

 Pseudomonas aeruginosa is a major nosocomial pathogen that causes severe disease including sepsis. Carbapenem-resistant P. aeruginosa is recognised by the World Health Organisation (WHO) as a priority 1 pathogen, with urgent need for new therapeutics.

As such, there is renewed interest in using bacteriophages as a therapeutic. However, the dynamics of treating pan-resistant P. aeruginosa with phage in vivo are poorly understood. Using a novel, pan-resistant P. aeruginosa in vivo infection model, phage therapy displayed strong therapeutic potential, clearing infection from the blood, kidneys, and spleen. Remaining bacteria in the lungs and liver displayed phage resistance due to limiting phage adsorption.

Yet, resistance to phage resulted in re-sensitisation to a wide range of antibiotics. Phage steering was utilised in vivo and pre-exposure with phage cocktail re-sensitised bacteria to tobramycin and meropenem, clearing the infection from all organs. Phage steering is an exciting potential alternative for treating pan-resistant P. aeruginosa infections