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PeerJ
2014;2 e590.

Synergy as a rationale for phage therapy using phage cocktails.

Matthew Schmerer, Ian J Molineux, James J Bull
Author Information
  1. Matthew Schmerer: Center for Computational Biology and Bioinformatics, The University of Texas at Austin , Austin, TX , USA.
  2. Ian J Molineux: Department of Molecular Biosciences, The University of Texas at Austin , Austin, TX , USA ; Institute for Cellular and Molecular Biology, The University of Texas at Austin , USA.
  3. James J Bull: Center for Computational Biology and Bioinformatics, The University of Texas at Austin , Austin, TX , USA ; Institute for Cellular and Molecular Biology, The University of Texas at Austin , USA ; Department of Integrative Biology, The University of Texas at Austin , USA.
PMID: 25279269 DOI: 10.7717/peerj.590

Abstract

Where phages are used to treat bacterial contaminations and infections, multiple phages are typically applied at once as a cocktail. When two or more phages in the cocktail attack the same bacterium, the combination may produce better killing than any single phage (synergy) or the combination may be worse than the best single phage (interference). Synergy is of obvious utility, especially if it can be predicted a priori, but it remains poorly documented with few examples known. This study addresses synergy in which one phage improves adsorption by a second phage. It first presents evidence of synergy from an experimental system of two phages and a mucoid E. coli host. The synergy likely stems from a tailspike enzyme produced by one of the phages. We then offer mathematical models and simulations to understand the dynamics of synergy and the enhanced magnitude of bacterial control possible. The models and observations complement each other and suggest that synergy may be of widespread utility and may be predictable from easily observed phenotypes.

Keywords

Bacteria Biofilm Depolymerase Dynamics Models Phage therapy

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Grants

  1. R01 GM057756/NIGMS NIH HHS
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