Belt and braces: Two escape ways to maintain the cassette reservoir of large chromosomal integrons

PLoS Genet. 2024 Apr 5;20(4):e1011231. doi: 10.1371/journal.pgen.1011231. eCollection 2024 Apr.

Abstract

Integrons are adaptive devices that capture, stockpile, shuffle and express gene cassettes thereby sampling combinatorial phenotypic diversity. Some integrons called sedentary chromosomal integrons (SCIs) can be massive structures containing hundreds of cassettes. Since most of these cassettes are non-expressed, it is not clear how they remain stable over long evolutionary timescales. Recently, it was found that the experimental inversion of the SCI of Vibrio cholerae led to a dramatic increase of the cassette excision rate associated with a fitness defect. Here, we question the evolutionary sustainability of this apparently counter selected genetic context. Through experimental evolution, we find that the integrase is rapidly inactivated and that the inverted SCI can recover its original orientation by homologous recombination between two insertion sequences (ISs) present in the array. These two outcomes of SCI inversion restore the normal growth and prevent the loss of cassettes, enabling SCIs to retain their roles as reservoirs of functions. These results illustrate a nice interplay between gene orientation, genome rearrangement, bacterial fitness and demonstrate how integrons can benefit from their embedded ISs.

MeSH terms

  • Bacteria* / genetics
  • DNA Transposable Elements
  • Integrases / genetics
  • Integrons* / genetics

Substances

  • DNA Transposable Elements
  • Integrases

Grants and funding

This work was supported by the Institut Pasteur (GAM, TC, DM), the Centre National de la Recherche Scientifique (CNRS-UMR 3525) (DM, CL), the Fondation pour la Recherche Médicale (FRM Grant No. EQU202103012569) (DM), the ANR Chromintevol (ANR-21-CE12-0002-01) (CL), the French Government’s Investissement d’Avenir program Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (ANR-10-LABX-62-IBEID) (DM), the Inception program (Investissement d’Avenir grant ANR-16-CONV-0005) (ER), the Ministère de l’Enseignement Supérieur et de la Recherche and the Direction Générale de l’Armement (DGA) (EL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.