Integron cassettes integrate into bacterial genomes via widespread non-classical attG sites

Loot, Céline; Millot, Gael A.; Richard, Egill; Littner, Eloi; Vit, Claire; Lemoine, Frédéric; Néron, Bertrand; Cury, Jean; Darracq, Baptiste; Niault, Théophile; Lapaillerie, Delphine; Parissi, Vincent; Rocha, Eduardo P. C.; Mazel, Didier

doi:10.1038/s41564-023-01548-y

Cited by 9 publications

(2 citation statements)

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“…( Top left ) A typical integron, with an integrase gene (magenta), a promoter (black), an attachment site ( attI ), and an already integrated cassette (blue); integrases (magenta pliers) catalyze the insertion or excision of gene cassettes (green) by recombining att sites. It was recently reported [ 203 ] that integrases can also insert/excise gene cassettes at other similar attachment sites in the genome ( attG ), where the cassette can express if a promoter is near, or can alter chromosomal genes. ( Top right ), the increasing roles of insertion sequences (ISs) in rearranging and mobilizing AR genes.…”

Section: Figurementioning

confidence: 99%

Non-Canonical Aspects of Antibiotics and Antibiotic Resistance

Amábile-Cuevas,

Lund-Zaina

2024

Antibiotics

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The understanding of antibiotic resistance, one of the major health threats of our time, is mostly based on dated and incomplete notions, especially in clinical contexts. The “canonical” mechanisms of action and pharmacodynamics of antibiotics, as well as the methods used to assess their activity upon bacteria, have not changed in decades; the same applies to the definition, acquisition, selective pressures, and drivers of resistance. As a consequence, the strategies to improve antibiotic usage and overcome resistance have ultimately failed. This review gathers most of the “non-canonical” notions on antibiotics and resistance: from the alternative mechanisms of action of antibiotics and the limitations of susceptibility testing to the wide variety of selective pressures, lateral gene transfer mechanisms, ubiquity, and societal factors maintaining resistance. Only by having a “big picture” view of the problem can adequate strategies to harness resistance be devised. These strategies must be global, addressing the many aspects that drive the increasing prevalence of resistant bacteria aside from the clinical use of antibiotics.

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Section: Figurementioning

confidence: 99%

Non-Canonical Aspects of Antibiotics and Antibiotic Resistance

Amábile-Cuevas,

Lund-Zaina

2024

Antibiotics

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“…Integrons are ancient genetic structures that play a crucial role in the spread of multidrug resistance in gram-negative bacteria and more generally in bacterial evolution [1][2][3][4]. These bacterial recombination systems can capture, store and shuffle small mobile elements-cassettesencoding adaptive functions.…”

Section: Introductionmentioning

confidence: 99%

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

Richard,

Darracq,

Littner

et al. 2024

PLoS Genet

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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.

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