Modeling the phage properties best for therapy

Abstract

The phages used to treat bacterial infections in phage therapy are commonly chosen based on their abilities to form plaques on the infecting bacterium - on host range. In practice, phage therapy is not always successful, leaving room for improvement. Here we use computational models to investigate whether some standard phage properties (burst size, lysis, adsorption, decay rate, growth rate) might serve as predictors of treatment success. As our measure of treatment success, we deviate from many other approaches by calculating the number of phage needed to suppress bacterial densities 100-fold in the short term, given that the patients immune system is expected to regain control once bacterial numbers are reduced. Numerical analysis of 2400 combinations of different values of phage phenotypes reveals that, on average, adsorption rate and growth rate provide the most useful predictive values, decay rate provides some value, whereas burst size and lysis time offer essentially little or no value. Bacterial density is especially informative of the number of phage required for treatment. There is nonetheless often considerable variation around average behavior for a single phenotype. These results raise the possibility that adsorption rate and growth rate may be especially important in phage therapy performance for both high and low bacterial densities. Given that therapeutic phages are often evolved in vitro for broad host ranges rather than for individual hosts, it should be considered that selection for broad host range may have a downside of compromising adsorption to and growth rate on individual bacterial hosts.