Details

Autor(en) / Beteiligte

• Subramanian , Ganapathy
• Subramanian, Ganapathy

Titel

Continuous Production of Bacteriophages

Ist Teil von

• Continuous Processing in Pharmaceutical Manufacturing, 2014, p.297-338

Ort / Verlag

Germany: Wiley

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Wiley Online Library All Obooks

Beschreibungen/Notizen

• As natural killers of bacteria, bacteriophages have been regaining importance in recent years due to increasing antibiotic resistance among bacteria. They are commonly very specific toward specific bacterial strains and they multiply faster than bacteria; therefore, rather low initial concentration is needed for efficient treatment. Bacteriophages multiply through the life cycle consisting of adsorption to bacterial cell, multiplication inside the cell, and then released into the media by cell lyses to start a new infection cycle. From each bacterial cell several hundred bacteriophages can be released. This number (commonly referred to as burst size), together with the duration between adsorption and lysis (named latent period) and the time needed for the bacteriophage to adsorb to the bacterial cell (described through adsorption constant), are key parameters defining bacteriophage multiplication and with that their production. Among many operation modes typically used in biotechnology processes, like batch, fed‐batch, and continuous that can provide the highest productivity gaining therefore on importance recently. In this chapter, two different experimental setups enabling continuous production, namely chemostat and cellstat, are extensively discussed. In chemostat, bacteria and bacteriophages are mixed together and therefore constantly exposed to selection pressure enhancing the mutation rate of both bacteria and bacteriophages. Because of this, chemostat experiments are almost indispensable in the study of resistance development and population dynamics, but are for the very same reason not suitable for long‐term robust production of bacteriophages. This issue is to most extent overcome in cellstat, which uses two connected bioreactors, cultivating only bacterial cells in the first bioreactor, which are then used as a substrate for bacteriophages multiplying in the second bioreactor. Since dilution rate in the second bioreactor is higher than the maximal specific growth rate of bacteria, bacterial mutations are not present. By properly adjusting bacteriophage–bacteria ratio minimizing selection pressure bacteriophage mutations are also mostly avoided. The parameters affecting cellstat productivity are extensively discussed and optimal productivity is derived. Technical challenges connected to long‐term continuous operation are considered together with different isolation techniques with emphasis on continuous purification.