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

Ashworth, Eleri A, Wright, Rosanna C T ORCID: https://orcid.org/0000-0002-8095-8256, Shears, Rebecca K ORCID: https://orcid.org/0000-0002-0279-2801, Wong, Janet K L, Hassan, Akram, Hall, James P J ORCID: https://orcid.org/0000-0002-4896-4592, Kadioglu, Aras and Fothergill, Joanne L ORCID: https://orcid.org/0000-0002-7012-1508 (2024) Exploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivo. Nature Communications, 15 (1). 1547. ISSN 2041-1723

Preview

Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview

Abstract

Pseudomonas aeruginosa is a major nosocomial pathogen that causes severe disease including sepsis. Carbapenem-resistant P. aeruginosa is recognised by the World Health Organisation 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 pan-resistant P. aeruginosa in vivo infection model, phage therapy displays strong therapeutic potential, clearing infection from the blood, kidneys, and spleen. Remaining bacteria in the lungs and liver displays phage resistance due to limiting phage adsorption. Yet, resistance to phage results in re-sensitisation to a wide range of antibiotics. In this work, we use phage steering in vivo, pre-exposing a pan resistant P. aeruginosa infection with a phage cocktail to re-sensitise bacteria to antibiotics, clearing the infection from all organs.