Continuous Production of Bacteriophages

Podgornik, Aleš; Janež, Nika; Smrekar, Franc; Peterka, Matjaž

doi:10.1002/9783527673681.ch12

Cited by 7 publications

(5 citation statements)

References 149 publications

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“…Therefore, we assumed that also term “d” is small enough to be neglected. Equation then simplifies into Equation (Podgornik et al., ).

λ = δ \cdot C (b \cdot e^{- L \cdot λ} - 1)

…”

Section: Introductionmentioning

confidence: 99%

“…However, pharmaceutical manufacturing is nowadays changing the trend from a batch to continuous production (Jungbauer, 2013;Lee et al, 2015). Thus, we can speculate that phage production for bacteriophage therapy will follow the same path in the future and new knowledge in this field is required (Podgornik, Janež, Smrekar, & Peterka, 2014). Chemostat is a bioreactor to which fresh medium is continuously added, while spent medium containing microorganisms, unconsumed nutrients and metabolic end products is removed at the same rate in order to keep the working volume constant (Novick & Szilard, 1950).…”

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confidence: 99%

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Effect of bacterial growth rate on bacteriophage population growth rate

2017

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It is important to understand how physiological state of the host influence propagation of bacteriophages (phages), due to the potential higher phage production needs in the future. In our study, we tried to elucidate the effect of bacterial growth rate on adsorption constant (δ), latent period (L), burst size (b), and bacteriophage population growth rate (λ). As a model system, a well‐studied phage T4 and Escherichia coli K‐12 as a host was used. Bacteria were grown in a continuous culture operating at dilution rates in the range between 0.06 and 0.98 hr−1. It was found that the burst size increases linearly from 8 PFU·cell−1 to 89 PFU·cell−1 with increase in bacteria growth rate. On the other hand, adsorption constant and latent period were both decreasing from 2.6∙10‐9 ml·min−1 and 80 min to reach limiting values of 0.5 × 10‐9 ml·min−1 and 27 min at higher growth rates, respectively. Both trends were mathematically described with Michaelis–Menten based type of equation and reasons for such form are discussed. By applying selected equations, a mathematical equation for prediction of bacteriophage population growth rate as a function of dilution rate was derived, reaching values around 8 hr−1 at highest dilution rate. Interestingly, almost identical description can be obtained using much simpler Monod type equation and possible reasons for this finding are discussed.

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“…Therefore, we assumed that also term “d” is small enough to be neglected. Equation then simplifies into Equation (Podgornik et al., ).

λ = δ \cdot C (b \cdot e^{- L \cdot λ} - 1)

…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of bacterial growth rate on bacteriophage population growth rate

2017

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“…Synchronization of the host in the first stage before infection led to improvements in the specific productivity of phages in the second stage while maintaining the volumetric productivity. Podgornik et al (2014) explained the process of bacteriophage multiplication and implemented it in their continuous production in bioreactors. Moreover, this work showed the mathematical model of production of bacteriophages in the continuous regime.…”

Section: Batch Systemmentioning

confidence: 99%

Chemical and Process Engineering

2022

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The practical applications of bacteriophages are associated with the problems related to the intensification, optimization of process production of this biomaterial and the search for new methods of production. The production of bacteriophages requires a fine balance between the dynamic growth of the bacteriophage and the host. The electromagnetic field (EMF) is a promising biotechnological method for the process production of bacteriophages. This study evaluates the use of various types of EMF to enhance the process. It was found that the process production of bacteriophages is divided into two stages. In the first stage, the influence of various types of EMF on the proliferation process of bacteria (host) was analyzed. Secondly, the process production of bacteriophage was implemented for the optimal infection conditions under the action of the various types of EMF. Moreover, the study demonstrated that the most effective bacteriophage production was the process with the application of the rotating magnetic field (RMF), pulsed magnetic field (PMF) and the static magnetic field (SMF) with negative polarity.

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“…Large scale phage propagations are commonly performed in bioreactor systems involving bacterial growth followed by phage infection within the same vessel 20 . This type of batch operation is considered inexpensive, simple, and robust, with short runs capable of yielding titers between 10 10 to 10 16 PFU/mL 3 , 21 , 37 . However, the long downtime periods in-between production runs that are necessary for proper cleaning and sterilization are significant disadvantages 3 .…”

Section: Introductionmentioning

confidence: 99%

Investigation into scalable and efficient enterotoxigenic Escherichia coli bacteriophage production

Wiebe,

Cook,

Lightly

et al. 2024

Sci Rep

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As the demand for bacteriophage (phage) therapy increases due to antibiotic resistance in microbial pathogens, strategies and methods for increased efficiency, large-scale phage production need to be determined. To date, very little has been published on how to establish scalable production for phages, while achieving and maintaining a high titer in an economical manner. The present work outlines a phage production strategy using an enterotoxigenic Escherichia coli-targeting phage, ‘Phage75’, and accounts for the following variables: infection load, multiplicity of infection, temperature, media composition, harvest time, and host bacteria. To streamline this process, variables impacting phage propagation were screened through a high-throughput assay monitoring optical density at 600 nm (OD600) to indirectly infer phage production from host cell lysis. Following screening, propagation conditions were translated in a scalable fashion in shake flasks at 0.01 L, 0.1 L, and 1 L. A final, proof-of-concept production was then carried out in a CellMaker bioreactor to represent practical application at an industrial level. Phage titers were obtained in the range of 9.5–10.1 log10 PFU/mL with no significant difference between yields from shake flasks and CellMaker. Overall, this suggests that the methodology for scalable processing is reliable for translating into large-scale phage production.

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Continuous Production of Bacteriophages

Cited by 7 publications

References 149 publications

Effect of bacterial growth rate on bacteriophage population growth rate

Effect of bacterial growth rate on bacteriophage population growth rate

Chemical and Process Engineering

Investigation into scalable and efficient enterotoxigenic Escherichia coli bacteriophage production

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