Computational design of phage cocktails based on phage-bacteria infection networks.

The misuse and overuse of antibiotics have boosted the proliferation of multidrug-resistant (MDR) bacteria, which are considered a major public health issue in the twenty-first century. Phage therapy may be a promising way in the treatment of infections caused by MDR pathogens, without the side effects of the current available antimicrobials. Phage therapy is based on phage cocktails, that is, combinations of phages able to lyse the target bacteria. In this work, we present and explain in detail two innovative computational methods to design phage cocktails taking into account a given phage-bacteria infection network. One of the methods (Exhaustive Search) always generates the best possible phage cocktail, while the other method (Network Metrics) always keeps a very reduced runtime (a few milliseconds). Both methods have been included in a Cytoscape application that is available for any user. A complete experimental study has been performed, evaluating and comparing the biological quality, runtime, and the impact when additional phages are included in the cocktail.