A SIMPL model of phage-bacteria interactions accounting for mutation and competition

Abstract

Pseudomonas aeruginosa is an opportunistically pathogenic bacteria that causes fatal infections and outbreaks in hospital environments. Due to the increasing prevalence of antibiotic-resistant strains of P. aeruginosa, the need for alternative therapies is critical. Bacteriophage therapy is emerging as a promising approach; however, it remains unapproved for clinical use and is hindered by limited understanding of the complex interactions between bacterial cells and phage virions. Mathematical models provide insight into these interactions. Through a system of ordinary differential equations, we determined necessary biological assumptions to effectively capture the dynamics observed between susceptible, infected, and mutated bacterial cells and bacteriophage virions in a microwell setting. Data fitting based on this model produced a set of parameter estimates unique to our experimental observations of a specific phage and P. aeruginosa strain. In translating observed optical density readings into bacterial concentrations, we also found that bacterial debris has a significant impact on optical density, with a lysed bacterium contributing roughly 31% as much to optical density readings as a living cell.