Bacteriophage resistant recombinant bacteria

摘要

Recombinant bacteria containing phage-encoded resistance ("Per") and methods of making and using the same are disclosed. Such bacteria are made by (a) conducting a fermentation of a substrate in a medium containing a defined bacterial culture until bacteriophage are detected in the medium, the bacteriophage being specific to at least one bacteria in the medium; (b) isolating the bacteriophage; (c) digesting DNA of the bacteriophage to produce a library of DNA fragments; (d) transforming the bacteria susceptible to said bacteriophage with the library of DNA fragments to provide transformed bacteria; (e) selecting from among the transformed bacteria, a bacteriophage-resistant transformed bacteria; (f) adding bacteriophage resistant transformed bacteria to the medium; and (g) recommencing step (a). Also disclosed are bacterial cells which contain a first bacteriophage defense mechanism (Per), wherein Per comprises a bacteriophage origin of replication (ori) operatively associated with a DNA sequence incapable of producing live bacteriophage. The bacterial cell is capable of being infected by a bacteriophage, the DNA of which, once injected into the bacterial cell, competes with Per for binding to DNA polymerase.