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Functional diversity increases the efficacy of phage combinations

View ORCID ProfileRosanna C. T. Wright, Ville-Petri Friman, Margaret C. M. Smith, Michael A. Brockhurst
doi: https://doi.org/10.1101/2021.07.09.451746
Rosanna C. T. Wright
1Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
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  • ORCID record for Rosanna C. T. Wright
  • For correspondence: rosanna.wright-2@manchester.ac.uk
Ville-Petri Friman
2Department of Biology, University of York, York, UK
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Margaret C. M. Smith
2Department of Biology, University of York, York, UK
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Michael A. Brockhurst
1Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
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Abstract

Phage therapy is a promising alternative to traditional antibiotics for treating bacterial infections. Such phage-based therapeutics typically contain multiple phages, but how the efficacy of phage combinations scales with phage richness, identity and functional traits is unclear. Here, we experimentally tested the efficacy of 827 unique phage combinations ranging in phage richness from 1 to 12 phages. The efficacy of phage combinations increased with phage richness. However, complementarity between functionally diverse phages allowed efficacy to be maximised at lower levels of phage richness in functionally diverse combinations. These findings suggest that phage functional diversity is the key property of effective phage combinations, enabling the design of simple but effective phage therapies that overcome the practical and regulatory hurdles that limit development of more diverse phage therapy cocktails.

Competing Interest Statement

The authors have declared no competing interest.

  • Abbreviations

    T4P
    Type IV Pilus
    LPS
    Lipopolysaccharide
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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    Posted July 09, 2021.
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    Functional diversity increases the efficacy of phage combinations
    Rosanna C. T. Wright, Ville-Petri Friman, Margaret C. M. Smith, Michael A. Brockhurst
    bioRxiv 2021.07.09.451746; doi: https://doi.org/10.1101/2021.07.09.451746
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    Functional diversity increases the efficacy of phage combinations
    Rosanna C. T. Wright, Ville-Petri Friman, Margaret C. M. Smith, Michael A. Brockhurst
    bioRxiv 2021.07.09.451746; doi: https://doi.org/10.1101/2021.07.09.451746

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