Phage Infections in Bioprocesses

The latest White Paper technical bulletin from bacteriophage experts Phage Consultants discusses strategies for preventing and managing bacteriophage infections in bacterial bioprocesses to maintain productivity in biotechnology facilities.

The White Paper ‘Minimization and Prevention of Phage Infections in Bioprocesses’ is authored by Phage Consultant CEO Prof. Dr. Marcin Łoś, who is one of the world’s foremost authorities on phage mechanisms and activity. It is based on a survey of existing literature and Phage Consultants’ extensive experience in this field.

Phage Infections in Biotech Facilities

Phage infections may bring a significant threat to the productivity of biotechnology facilities, leading to potential financial losses. ​Understanding the sources and prevention methods for phage contamination is crucial for maintaining efficient bioprocesses. ​

It details the main risk factors that include:

• Facility Location: Risk of phage contamination increases when facilities are placed in environments that harbor target bacterial species, such as water treatment plants and areas with manure usage.
• Contamination Sources: Phages can enter bioprocesses through various sources, such as air used for aeration, unsterilized raw materials, hard-to-clean areas of equipment and plant.
• Inadequate personnel training: Operators can inadvertently introduce phages via clothing, footwear, etc.
• Bacterial Strains: The choice of bacterial strains can influence susceptibility to phage infections. ​ While some strains exhibit resistance, this is not a foolproof solution. ​ Continuous monitoring and proper strain selection are necessary for long-term protection.

Phage Contamination Dynamics

Phage contamination can be categorized into primary and secondary infections, each with distinct characteristics and implications for bioprocesses. ​

• Primary contamination originates from external sources and may not immediately affect fermentation. ​ Seasonal factors can influence the likelihood of primary contamination, with wet conditions facilitating phage spread. ​
• Secondary contamination occurs when primary contamination is not prevented from spreading in facilities often leading to more severe outbreaks and decreasing the chances of favorable fermentations.​

Phage Detection and Monitoring Techniques

Effective detection of phages is crucial for managing contamination in fermentation processes. ​Various methods exist, each with its own advantages and limitations.

• Double layer agar plates are commonly used for phage detection but can yield false negatives. ​
• Rapid detection methods are available but possible only for well-characterized phages. ​
• Regular monitoring and testing are essential to identify phage presence before outbreaks occur. ​

Phage Eradication Strategies

Eradicating phages from a facility requires a combination of effective cleaning, sterilization, and monitoring strategies. ​ Proper facility design can significantly aid this process.

• Disinfectants must be chosen carefully, as not all are effective against phages. ​
• Heat treatment can be effective, but the method of application is critical for success.
• Regular testing post-decontamination is necessary to ensure phage absence. ​
• Emergency procedures should be established to respond quickly to contamination events.

​The White Paper includes 30 scientific references that span the range of knowledge on phage contaminations from the 1950s onwards. In summary, it shows that protecting industrial bioprocesses from bacteriophage contamination involves a combination of plant design, operating procedures, regular testing and effective emergency plans.

Resources

Click on Minimization and Prevention of Phage Infections in Bioprocesses to access paper on Springer Nature.