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

Fothergill, Joanne ORCID: 0000-0002-7012-1508, Kadioglu, Aras ORCID: 0000-0003-1137-6321 and Hall, James ORCID: 0000-0002-4896-4592 (2024) Exploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivo. Nature Communications, 15 (1). 1547-.

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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.

Item Type:	Article
Uncontrolled Keywords:	Lung, Humans, Pseudomonas aeruginosa, Bacteriophages, Pseudomonas Infections, Anti-Bacterial Agents, Phage Therapy
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	15 Feb 2024 16:39
Last Modified:	07 Mar 2024 08:07
DOI:	10.1038/s41467-024-45785-z
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3178673