CULTURES WITH IMPROVED PHAGE RESISTANCE

摘要

Disclosed is a method for generating at least one bacteriophage resistant variant strain, comprising the steps of: (a) exposing a parent bacterial strain comprising at least a portion of a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) locus to at least a first bacteriophage nucleic acid sequence to produce a mixture of bacteria comprising at least one bacteriophage resistant variant strain comprising a modified CRISPR locus; and (b) isolating said at least one bacteriophage resistant variant strain, wherein said strain comprises an additional nucleic acid fragment in said modified CRISPR locus; wherein during generation of said bacteriophage resistant variant strain, said parent bacterial strain is exposed to two or more bacteriophage nucleic acid sequences and exposure to at least a second nucleic acid sequence occurs either (i) simultaneously with exposure to the first nucleic acid sequence in step (a), or (ii) subsequent to step (a).