Patent-family-91406943

Provided herein are compositions for achieving native adaptive spacer acquisition in an unadapted CRISPR-Cas system, such as a non-adaptive lactococcus CRISPR-Cas system. Methods of using these compositions and products thereof to produce bacterial strains that are resistant, such as bacteriophage resistance, and/or evolve to have a desired phenotype are also provided. Also provided are non-adaptive CRISPR-Cas systems adapted according to the methods provided herein, and bacteria containing such adapted non-adaptive CRISPR-Cas systems. The compositions and methods provided herein allow for controlled induction of the gain of a natural spacer via fundamental features that adapt in a CRISPR-Cas system that is substantially non-adaptable without altering the non-adaptive behavior of the CRISPR-Cas system.