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  • Review Article
  • Published:

Integrons: agents of bacterial evolution

Nature Reviews Microbiology volume 4, pages 608–620 (2006)Cite this article

Key Points

  • Integrons are assembly platforms that incorporate exogenous open reading frames through site-specific recombination and convert them to functional genes by ensuring their correct expression.

  • Although integrons were discovered through their involvement in the development of multiple antibiotic resistance in Gram-negative pathogens when carried in transposons, their role in genome evolution has been extended with the discovery of other, often larger, integron structures as genuine components of the genomes of many γ-proteobacterial species.

  • This Review discusses the structural differences among the different types of integron — those carried in mobile DNA elements and the chromosomal superintegrons — as well as their evolutionary history and phylogenetic relationships.

  • The different functions encoded by the integron gene cassettes are reviewed, with emphasis on those from superintegrons and other chromosomal integrons from environmental bacteria.

  • The dynamics of the intraspecies and interspecies variation of the large cassette arrays of superintegrons, and their role in the increase in antibiotic resistance, are discussed.

  • Finally, the specific recombination reactions occurring in these elements are reviewed, and a novel model involving a single-stranded substrate for recombination for cassette insertion and deletion is proposed.

Abstract

Integrons are assembly platforms — DNA elements that acquire open reading frames embedded in exogenous gene cassettes and convert them to functional genes by ensuring their correct expression. They were first identified by virtue of their important role in the spread of antibiotic-resistance genes. More recently, our understanding of their importance in bacterial genome evolution has broadened with the discovery of larger integron structures, termed superintegrons. These DNA elements contain hundreds of accessory genes and constitute a significant fraction of the genomes of many bacterial species. Here, the basic biology of integrons and superintegrons, their evolutionary history and the evidence for the existence of a novel recombination pathway is reviewed.

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Figure 1: Mobile integrons and superintegrons.
Figure 2: Phylogenetic relationship of the integron intI genes in the proteobacteria.
Figure 3: Integron recombination sites.
Figure 4: A model of integron-mediated recombination.
Figure 5: Architecture of an integrase–Vibrio cholerae repeat (VCR) synapse.

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Acknowledgements

Work in the Mazel laboratory was supported by the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS), the Programme de Recherche en Microbiologie (from the Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche; MENESR), the Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER) and the European Union Collective Research on Aquaculture Biofouling (CRAB) consortium and Network of Excellence EuroPathoGenomics).

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  1. Department Génomes et Génétiqu, Unité Plasticité du Génome Bactérien- CNRS URA 2171, Institut Pasteur, 25 rue du Dr Roux, Paris, 75724, France

    Didier Mazel

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DATABASES

Entrez Genome Project

Escherichia coli

Nitrosomonas europaea

Photobacterium profundum

Proteus mirabilis

Pseudomonas stutzeri

Rhodopirellula baltica

Salmonella enterica

Shewanella oneidensis

Shigella dysenteriae

Treponema denticola

Vibrio cholerae

Vibrio fischeri

Vibrio parahaemolyticus

Vibrio salmonicida

Vibrio vulnificus

Xanthomonas campestris

FURTHER INFORMATION

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Glossary

Transposon

A mobile DNA element that can relocate within the genome of its host.

Insertion sequence

(IS) A small (<2.5 kb), generally phenotypically cryptic segment of DNA that has a simple organization and is capable of insertion at multiple sites in a _target DNA molecule. Examples include IS1, IS608 and IS911.

Conjugative plasmid

A plasmid that can move from one cell to another during the process of conjugation.

SXT element

Vibrio cholerae-derived integrating and conjugative element (also referred to as a conjugative transposon or constin).

Compound transposon

A segment of DNA flanked by two similar insertion sequences, in direct or inverted orientations. Examples include Tn5 and Tn10.

Transposase

The enzyme that promotes cutting of the DNA at the ends of a transposable element and joining to the DNA molecule into which the element is to be inserted.

Transposon-mutagenesis screen

The use of transposons to generate (knock-out) mutations.

Nudix hydrolases

Nudix hydrolases (nucleoside diphosphate linked to some other moiety X) are enzymes that hydrolyse diverse nucleoside diphosphate or triphosphate derivatives.

Toxin–antitoxin families

Paired loci found in the chromosomes of almost all free-living bacteria, and many plasmids and phage genomes. They encode a toxin and its antidote, which have been shown to contribute to plasmid stability by a mechanism called post-segregational killing and are also proposed to function in bacterial programmed cell death or stress physiology.

Minimum inhibitory concentration

The lowest concentration of an antibiotic that inhibits growth of the organism.

Co-integrates

The structural fusion of replicons through a recombination reaction.

Holliday junction

A point at which the strands of two double-stranded DNA molecules exchange partners, which occurs as an intermediate in genetic recombination.

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Mazel, D. Integrons: agents of bacterial evolution. Nat Rev Microbiol 4, 608–620 (2006). https://doi.org/10.1038/nrmicro1462

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  • DOI: https://doi.org/10.1038/nrmicro1462

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