Cassette recombination dynamics within chromosomal integrons are regulated by toxin-antitoxin systems

Author:

Richard Egill12ORCID,Darracq Baptiste12ORCID,Littner Eloi234ORCID,Vit Claire12,Whiteway Clémence1ORCID,Bos Julia1ORCID,Fournes Florian1ORCID,Garriss Geneviève1ORCID,Conte Valentin1ORCID,Lapaillerie Delphine56ORCID,Parissi Vincent56ORCID,Rousset François7,Skovgaard Ole8ORCID,Bikard David7ORCID,Rocha Eduardo P. C.3ORCID,Mazel Didier1ORCID,Loot Céline1ORCID

Affiliation:

1. Institut Pasteur, Université Paris Cité, CNRS UMR3525, Unité Plasticité du Génome Bactérien, 75015 Paris, France.

2. Sorbonne Université, ED515, F-75005 Paris, France.

3. Institut Pasteur, Université Paris Cité, CNRS UMR3525, Microbial Evolutionary Genomics, 75015 Paris, France.

4. DGA CBRN Defence, 91710 Vert-le-Petit, France.

5. University of Bordeaux, Fundamental Microbiology and Pathogenicity Laboratory, CNRS, UMR 5234, SFR TransBioMed, Bordeaux, France.

6. Viral DNA Integration and Chromatin Dynamics Network (DyNAVir), France.

7. Institut Pasteur, Université Paris Cité, CNRS UMR6047, Synthetic Biology, 75015 Paris, France.

8. Department of Science, Systems and Models, Roskilde University, Roskilde DK-4000, Denmark.

Abstract

Integrons are adaptive bacterial devices that rearrange promoter-less gene cassettes into variable ordered arrays under stress conditions, thereby sampling combinatorial phenotypic diversity. Chromosomal integrons often carry hundreds of silent gene cassettes, with integrase-mediated recombination leading to rampant DNA excision and integration, posing a potential threat to genome integrity. How this activity is regulated and controlled, particularly through selective pressures, to maintain such large cassette arrays is unknown. Here, we show a key role of promoter-containing toxin-antitoxin (TA) cassettes as systems that kill the cell when the overall cassette excision rate is too high. These results highlight the importance of TA cassettes regulating the cassette recombination dynamics and provide insight into the evolution and success of integrons in bacterial genomes.

Publisher

American Association for the Advancement of Science (AAAS)

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