Bacteriophages are bacterial viruses which are amplified during the process of infection and final lysis of bacteria. Amplification of bacteriophages on laboratory scale in shaking culture flasks is a routine procedure but for clinical applications higher titers and amount of bacteriophages are needed (1). Significantly higher concentration of bacteriophages and better yields were first obtained by batch culture and later on with continuous production of bacteriophages in bioreactors. At the beginning, chemostat was mainly used, but later on trend switched to usage of cellstat due to observed occurrence of mutations in bacteria and bacteriophages as well (2). Cellstat consists of two connected bioreactors. Bacteria is continuously growing in first bioreactor and is then introduced into second bioreactor where multiplication of bacteriophages occurs (3). As dilution factor in first bioreactor determines bacteria specific growth rate and by this its condition, this seems to be a powerful tool for studying the effect of bacteria physiological state on bacteriophage multiplication. Efficiency of bacteriophage infection was studied through adsorption constant, latent period and burst size using bacteria growing in first bioreactor varying dilution rate. Obtained values were used for prediction of cellstat productivity in continuous mode.

Literature:
1. Merabishvili M., Pirnay J.P., Verbeken G., Chanishvili N., Tediashvili M., et al. 2009. Quality-Controlled Small-Scale Production of a Well-Defined Bacteriophage Cocktail for Use in Human Clinical Trials. PLoS ONE, 4, 3: e4944
2. Podgornik, A., Janež, N., Smrekar, F., Peterka, M. 2014. Continuous Production of Bacteriophages, in Continuous Processing in Pharmaceutical Manufacturing (ed G. Subramanian), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany.
3. Husimi, Y., Nishigaki, K., Kinoshita, Y., Tanaka, T. 1982. Cellstat-A continuous culture system of a bacteriophage for the study of the mutation rate and the selection process at the DNA level. Review of scientific instruments, 53: 517-522