Bacteriophages are viruses that multiply through the infection of specific bacteria and can be used to treat bacterial infections. In the industry, bacteriophages are produced in batch bioreactors, but because we expect more and more interest in the future, due to increasing antibiotic resistance, continuous cultivation is a good alternative to the current form of production. Cellstat is a continuous stirred tank system consisting of two connected bioreactors with constant media flow. In the first bioreactor, we cultivated bacterial culture without presence of bacteriophages and maintained constant bacterial physiological state. In the second bioreactor, bacteriophages are propagated with constant flow of bacteria from first bioreactor. The dilution rate is regulated by lowering the volume of the medium in the second bioreactor. By changing the dilution rate, we regulate the bacteriophage reproduction, which can be described as bacteriophage fitness and connects three key growth parameters: burst size, latent period and adsorption constant. By increasing dilution rate in the second bioreactor during bacteriophage production, bacteriophages with higher fitness are obtained. Bacteriophages adapt to new conditions with increased burst size and shorter latent period. Reproduction itself is also strongly depended on the physiological state cultivation conditions of bacteria and this affects the extent to which bacteriophage adaptation is possible.
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