Genetic drivers of chromosomal integron stability

Abstract

AbstractThe integron is a bacterial recombination system that allows acquisition, stockpiling and expression of promoterless genes embedded in cassettes. Some integrons, like the one found in the second chromosome ofVibrio cholerae, can be particularly massive, gathering hundreds of non-expressed cassettes. It is unclear how such genetic structures can be stabilized in bacterial genomes. Here, we reveal that the orientation of integrons toward replication within bacterial chromosomes is essential to their stability. Indeed, we show that upon inversion of theV. choleraechromosomal integron, the cassette excision rate of its cassettes is dramatically increased. This correlates with a strong growth defect which we show is mostly due to the excision of a remarkable type of cassettes bearing their own promoter and encoding toxin– antitoxin systems. This “abortive excision” of toxin–antitoxin systems can prevent the inversion of chromosomal integrons and the associated extensive loss of cassettes. Our analysis of the available sedentary chromosomal integrons in genome database show an over-representation of toxin–antitoxin cassettes in large integrons. This study thus provides a striking example of the relationship between genome organization, genome stability and an emerging property of toxin–antitoxin systems.