Effect of dilution rate on productivity of continuous bacteriophage production in cellstat

Ability to efficiently propagate high quantities of bacteriophages (phages) is of great importance considering higher phage production needs in the future. Continuous production of phages could represent an interesting option. In our study, we tried to elucidate the effect of dilution rate on productivity of continuous production of phages in cellstat. As a model system, a well-studied phage T4 and Escherichia coli K-12 as a host were used. Experiments where physiology of bacteria was changing with dilution rate of cellstat and where bacterial physiology was kept constant were performed. For both setups there exists an optimal dilution rate when maximal productivity is achieved. Experimentally obtained values of phage concentration and corresponding productivity were compared with mathematical model predictions, and good agreement was obtained for both types of experiments. Analysis of mathematical model coefficients revealed that latent period and burst size to dilution rate coefficient mostly affect optimum dilution rate and productivity. Due to high sensitivity, it is important to evaluate phage growth parameters carefully, to run cellstat under optimal productivity.