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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Vydáno v:	Nature communications Ročník 15; číslo 1; s. 8572 - 18
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 03.10.2024 Nature Publishing Group Nature Portfolio
Témata:	147/135 147/143 38/22 38/23 38/44 38/77 42 631/1647/2234 631/181/2475 631/326/1321 631/326/46 692/699/255/1318 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
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-52595-w