Center of Excellence for Biosensors, Instrumentation and Process Control (COBIK), Tovarniška cesta 26, Ajdovščina, Slovenia.
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, Ljubljana, Slovenia.
Appl Microbiol Biotechnol. 2018 Apr;102(8):3649-3661. doi: 10.1007/s00253-018-8893-9. Epub 2018 Mar 7.
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.
考虑到未来更高的噬菌体（phages）生产需求，高效繁殖大量噬菌体具有重要意义。连续生产噬菌体可能是一个有趣的选择。在我们的研究中，我们试图阐明稀释率对细胞培养连续生产噬菌体生产力的影响。作为模型系统，我们使用了一种研究充分的噬菌体 T4 和大肠杆菌 K-12 作为宿主。我们进行了实验，其中细胞培养的稀释率改变了细菌的生理状态，同时保持了细菌的生理状态不变。对于这两种设置，当达到最大生产力时，都存在最佳的稀释率。实验获得的噬菌体浓度值和相应的生产力与数学模型预测值进行了比较，两种类型的实验都得到了很好的一致性。对数学模型系数的分析表明，潜伏期和爆发大小与稀释率系数对最佳稀释率和生产力影响最大。由于高灵敏度，在最佳生产力下运行细胞培养时，仔细评估噬菌体生长参数非常重要。
