Engineered bacteriophage-defence systems in bioprocessing

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Abstract
Bacteriophages (phages) can devastate bacterial strains that are used in fermentations and bioprocesses. Comparative genomic analyses can be used to streamline the construction of genetic systems that are designed to protect bioprocessing strains against phage attack. Gene-silencing techniques, such as antisense-RNA targeting of essential phage-encoded genes (for example, DNA replication) can effectively inhibit the propagation of virulent phages. Trans-dominant negative mutant proteins that are derived from phage-encoded genes can be used to sabotage the function of multimeric phage–protein complexes by a process called subunit poisoning. The native role of some phage-encoded genes is to protect lysogens against superinfecting phages. Such genes can also be exploited to protect non-lysogenic bioprocessing cultures from superinfection (for example, superinfection exclusion or immunity). Selected engineered systems have been composed of phage-encoded cis regulatory elements, such as phage origins of DNA replication or phage promoters that drive abortive or suicide systems in the infected cell (for example, phage-triggered suicide systems).