Structure-specific DNA recombination sites: Design, validation, and machine learning–based refinement

Nivina, Aleksandra; Grieb, Maj Svea; Loot, Céline; Bikard, David; Cury, Jean; Shehata, Laila; Bernardes, Juliana Silva; Mazel, Didier

doi:10.1126/sciadv.aay2922

Cited by 20 publications

(20 citation statements)

References 48 publications

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“…The former has already been exquisitely demonstrated [64]. Applications of recombinationbased genetic engineering tools are limited by the requirement of high sequence specificity of recombination sites.…”

Section: Integrons As a Biotechnological Resourcementioning

confidence: 99%

“…Applications of recombinationbased genetic engineering tools are limited by the requirement of high sequence specificity of recombination sites. To overcome this, Nivina et al [64] designed synthetic attC sites in silico, and used these as highly efficient, sequence-independent recombination sites for genomic engineering. As attCs rely on their folding structure to act as recombination substrates, they exhibit very minimal sequence-level constraints.…”

Section: Integrons As a Biotechnological Resourcementioning

confidence: 99%

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The Natural History of Integrons

et al. 2021

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Integrons were first identified because of their central role in assembling and disseminating antibiotic resistance genes in commensal and pathogenic bacteria. However, these clinically relevant integrons represent only a small proportion of integron diversity. Integrons are now known to be ancient genetic elements that are hotspots for genomic diversity, helping to generate adaptive phenotypes. This perspective examines the diversity, functions, and activities of integrons within both natural and clinical environments. We show how the fundamental properties of integrons exquisitely pre-adapted them to respond to the selection pressures imposed by the human use of antimicrobial compounds. We then follow the extraordinary increase in abundance of one class of integrons (class 1) that has resulted from its acquisition by multiple mobile genetic elements, and subsequent colonisation of diverse bacterial species, and a wide range of animal hosts. Consequently, this class of integrons has become a significant pollutant in its own right, to the extent that it can now be detected in most ecosystems. As human activities continue to drive environmental instability, integrons will likely continue to play key roles in bacterial adaptation in both natural and clinical settings. Understanding the ecological and evolutionary dynamics of integrons can help us predict and shape these outcomes that have direct relevance to human and ecosystem health.

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Section: Integrons As a Biotechnological Resourcementioning

confidence: 99%

Section: Integrons As a Biotechnological Resourcementioning

confidence: 99%

The Natural History of Integrons

et al. 2021

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“…That is, tandem arrays of short open reading frames (ORFs), generally in the same orientation, interspersed by attC recombination sites. Archaeal attCs exhibit the same single-stranded folding structure as bacterial attCs, which is essential for them to act as structure-specific DNA recombination sites [25][26][27][28][29][30][31] . We also note that archaeal IntIs exhibit the defining characteristics of bacterial IntIs, being tyrosine recombinases that possess a unique IntI-specific additional domain surrounding the patch III motif region necessary for integron-mediated recombination 32 .…”

Section: Genetic Structure Of Archaeal Integronsmentioning

confidence: 99%

Discovery of integrons in Archaea: platforms for cross-domain gene transfer

Ghaly

Tetu

Penesyan

et al. 2022

Preprint

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Horizontal gene transfer between different domains of life is increasingly being recognised as an important driver of evolution, with the potential to provide the recipient with new gene functionality and assist niche adaptation1-3. However, the molecular mechanisms underlying the integration of exogenous genes from foreign domains are mostly unknown. Integrons are a family of genetic elements that facilitate this process within Bacteria via site-specific DNA recombination4-7. Integrons, however, have not been reported outside Bacteria, and thus their potential role in cross-domain gene transfer has not been investigated. Here we show that integrons are also present among diverse phyla within the domain Archaea. Further, we provide experimental evidence that integron-mediated recombination can facilitate the recruitment of archaeal genes by bacteria. Our findings establish a new mechanism that can facilitate horizontal gene transfer between the two domains of prokaryotes, which has important implications for prokaryotic evolution in both clinical and environmental contexts.

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“…Some strategies were designed to recognize attC sites of “classical” integrons (Stokes et al, 2001 ), although this is difficult because they exhibit a relatively high diversity (Cury et al, 2016 ). This has even allowed for encryption of these sequences within protein‐coding sequences (Nivina et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Metagenomic strategies identify diverse integron‐integrase and antibiotic resistance genes in the Antarctic environment

Antelo

Giménez

Azziz³

et al. 2021

MicrobiologyOpen

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The objective of this study is to identify and analyze integrons and antibiotic resistance genes (ARGs) in samples collected from diverse sites in terrestrial Antarctica. Integrons were studied using two independent methods. One involved the construction and analysis of intI gene amplicon libraries. In addition, we sequenced 17 metagenomes of microbial mats and soil by high‐throughput sequencing and analyzed these data using the IntegronFinder program. As expected, the metagenomic analysis allowed for the identification of novel predicted intI integrases and gene cassettes (GCs), which mostly encode unknown functions. However, some intI genes are similar to sequences previously identified by amplicon library analysis in soil samples collected from non‐Antarctic sites. ARGs were analyzed in the metagenomes using ABRIcate with CARD database and verified if these genes could be classified as GCs by IntegronFinder. We identified 53 ARGs in 15 metagenomes, but only four were classified as GCs, one in MTG12 metagenome (Continental Antarctica), encoding an aminoglycoside‐modifying enzyme (AAC(6´)acetyltransferase) and the other three in CS1 metagenome (Maritime Antarctica). One of these genes encodes a class D β‐lactamase (blaOXA‐205) and the other two are located in the same contig. One is part of a gene encoding the first 76 amino acids of aminoglycoside adenyltransferase ( aadA6 ), and the other is a qacG2 gene.

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Structure-specific DNA recombination sites: Design, validation, and machine learning–based refinement

Cited by 20 publications

References 48 publications

The Natural History of Integrons

The Natural History of Integrons

Discovery of integrons in Archaea: platforms for cross-domain gene transfer

Metagenomic strategies identify diverse integron‐integrase and antibiotic resistance genes in the Antarctic environment

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