Postreplication targeting of transformants by bacterial immune systems?

• Bacterial restriction–modification and CRISPR immune systems limit natural transformation.
• Transformation relies on exogenous single-stranded DNA, resistant to these systems.
• We propose a common mechanism for destruction of potential transformants by immune systems.
• This involves attack of transformed chromosomes following restoration of double strandedness by replication.

Bacteria are constantly challenged by foreign genetic elements such as bacteriophages and plasmids. Several defense systems provide immunity against such attackers, including restriction–modification (R–M) systems and clustered, regularly interspaced short palindromic repeats (CRISPRs). These systems target attacking DNA and thus antagonize natural transformation, which relies on uptake of exogenous DNA to promote acquisition of new genetic traits. It is unclear how this antagonization occurs, because transforming DNA is single stranded, and thus resistant to these immune systems. Here, we propose a simple model whereby these systems limit transformation by attack of transformed chromosomes once double strandedness is restored by chromosomal replication.