Targeting Pseudomonas aeruginosa biofilm with an evolutionary trained bacteriophage cocktail exploiting phage resistance trade-offs

Spread of multidrug-resistant Pseudomonas aeruginosa strains threatens to render currently available antibiotics obsolete, with limited prospects for the development of new antibiotics. Lytic bacteriophages, the viruses of bacteria, represent a path to combat this threat. In vitro-directed evolution...

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Bibliographic Details
Published in:Nature communications Vol. 15; no. 1; pp. 8572 - 18
Main Authors: Kunisch, Fabian, Campobasso, Claudia, Wagemans, Jeroen, Yildirim, Selma, Chan, Benjamin K., Schaudinn, Christoph, Lavigne, Rob, Turner, Paul E., Raschke, Michael J., Trampuz, Andrej, Gonzalez Moreno, Mercedes
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 03.10.2024
Nature Publishing Group
Nature Portfolio
Subjects:
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631/1647/2234
631/181/2475
631/326/1321
631/326/46
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Anti-Bacterial Agents - pharmacology
Antibiotics
Assaying
Bacteria
Bacterial diseases
Bacterial infections
Bacteriophages - genetics
Bacteriophages - physiology
Biofilms
Biofilms - growth & development
Design optimization
Directed evolution
Drug Resistance, Multiple, Bacterial
Effectiveness
Evolution
Host range
Host Specificity
Humanities and Social Sciences
Humans
Microbial Sensitivity Tests
Microorganisms
multidisciplinary
Multidrug resistance
Phage Therapy - methods
Phages
Polymerase chain reaction
Pseudomonas aeruginosa
Pseudomonas aeruginosa - drug effects
Pseudomonas aeruginosa - physiology
Pseudomonas aeruginosa - virology
Pseudomonas Infections - microbiology
Pseudomonas Infections - therapy
Pseudomonas Phages - genetics
Pseudomonas Phages - physiology
Science
Science (multidisciplinary)
Tradeoffs
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Spread of multidrug-resistant Pseudomonas aeruginosa strains threatens to render currently available antibiotics obsolete, with limited prospects for the development of new antibiotics. Lytic bacteriophages, the viruses of bacteria, represent a path to combat this threat. In vitro-directed evolution is traditionally applied to expand the bacteriophage host range or increase bacterial suppression in planktonic cultures. However, while up to 80% of human microbial infections are biofilm-associated, research towards targeted improvement of bacteriophages’ ability to combat biofilms remains scarce. This study aims at an in vitro biofilm evolution assay to improve multiple bacteriophage parameters in parallel and the optimisation of bacteriophage cocktail design by exploiting a bacterial bacteriophage resistance trade-off. The evolved bacteriophages show an expanded host spectrum, improved antimicrobial efficacy and enhanced antibiofilm performance, as assessed by isothermal microcalorimetry and quantitative polymerase chain reaction, respectively. Our two-phage cocktail reveals further improved antimicrobial efficacy without incurring dual-bacteriophage-resistance in treated bacteria. We anticipate this assay will allow a better understanding of phenotypic-genomic relationships in bacteriophages and enable the training of bacteriophages against other desired pathogens. This, in turn, will strengthen bacteriophage therapy as a treatment adjunct to improve clinical outcomes of multidrug-resistant bacterial infections. Using a biofilm evolution assay, this study improves the antimicrobial and antibiofilm efficacy of Pseudomonas aeruginosa bacteriophages, while a two-phage cocktail shows further improved antimicrobial efficacy without incurring dual-bacteriophage-resistance.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-52595-w