The addition of therapeutic phage to treat Multi-Drug Resistant (MDR) pathogens imposes a strong selective pressure for the emergence of phage-resistant bacteria. Modeling and in vivo experiments have established that phage-resistant bacteria proliferate in Myd88-/- (immunodeficient) mice, corresponding to a failure of phage therapy. This work aims to develop evolutionarily robust phage therapy in immunodeficient hosts. First, we consider a model where bacteria evolve in an abstract discrete phenotypic space against different types of phages present in a therapeutic phage library. Second, we formulate a single-dose optimization problem subject to the proposed eco-evolutionary dynamics. The goal is to minimize the total bacterial population while penalizing the treatment costs by optimizing the phage therapy administrations. Finally, we extend single-dose treatment to multi-dose treatment and find the optimal policy via control theory. 

This seminar will be hosted at this bluejeans link.