Exploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivo
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 b...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45785-z |
| _version_ | 1827327021981630464 |
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| author | Eleri A. Ashworth Rosanna C. T. Wright Rebecca K. Shears Janet K. L. Wong Akram Hassan James P. J. Hall Aras Kadioglu Joanne L. Fothergill |
| author_facet | Eleri A. Ashworth Rosanna C. T. Wright Rebecca K. Shears Janet K. L. Wong Akram Hassan James P. J. Hall Aras Kadioglu Joanne L. Fothergill |
| author_sort | Eleri A. Ashworth |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:53:57Z |
| format | Article |
| id | doaj.art-d7674a4d2b9846549863382aa65c4b86 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:53:57Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d7674a4d2b9846549863382aa65c4b862024-03-05T19:33:56ZengNature PortfolioNature Communications2041-17232024-02-0115111610.1038/s41467-024-45785-zExploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivoEleri A. Ashworth0Rosanna C. T. Wright1Rebecca K. Shears2Janet K. L. Wong3Akram Hassan4James P. J. Hall5Aras Kadioglu6Joanne L. Fothergill7Department of Clinical Infection, Microbiology and Immunology, University of LiverpoolDivision of Evolution & Genomic Sciences, School of Biological Sciences, University of ManchesterDepartment of Clinical Infection, Microbiology and Immunology, University of LiverpoolDepartment of Clinical Infection, Microbiology and Immunology, University of LiverpoolDepartment of Clinical Infection, Microbiology and Immunology, University of LiverpoolDepartment of Evolution, Ecology and Behaviour, University of LiverpoolDepartment of Clinical Infection, Microbiology and Immunology, University of LiverpoolDepartment of Clinical Infection, Microbiology and Immunology, University of LiverpoolAbstract 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.https://doi.org/10.1038/s41467-024-45785-z |
| spellingShingle | Eleri A. Ashworth Rosanna C. T. Wright Rebecca K. Shears Janet K. L. Wong Akram Hassan James P. J. Hall Aras Kadioglu Joanne L. Fothergill Exploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivo Nature Communications |
| title | Exploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivo |
| title_full | Exploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivo |
| title_fullStr | Exploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivo |
| title_full_unstemmed | Exploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivo |
| title_short | Exploiting lung adaptation and phage steering to clear pan-resistant Pseudomonas aeruginosa infections in vivo |
| title_sort | exploiting lung adaptation and phage steering to clear pan resistant pseudomonas aeruginosa infections in vivo |
| url | https://doi.org/10.1038/s41467-024-45785-z |
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