Overcoming Bacteriophage Contamination in Bioprocessing: Strategies and Applications

Abstract Bacteriophage contamination has a devastating impact on the viability of bacterial hosts and can significantly reduce the productivity of bioprocesses in biotechnological industries. The consequences range from widespread fermentation failure to substantial economic losses, highlighting the urgent need for effective countermeasures. Conventional prevention methods, which focus primarily on the physical removal of bacteriophages from equipment, bioprocess units, and the environment, have proven ineffective in preventing phage entry and contamination. The coevolutionary dynamics between phages and their bacterial hosts have spurred the development of a diverse repertoire of antiviral defense mechanisms within microbial communities. These naturally occurring defense strategies can be harnessed through genetic engineering to convert phage‐sensitive hosts into robust, phage‐resistant cell factories, providing a strategic approach to mitigate the threats posed by bacteriophages to industrial bacterial processes. In this review, an overview of the various defense strategies and immune systems that curb the propagation of bacteriophages and highlight their applications in fermentation bioprocesses to combat phage contamination is provided. Additionally, the tactics employed by phages to circumvent these defense strategies are also discussed, as preventing the emergence of phage escape mutants is a key component of effective contamination management.