Integrons as Adaptive Devices
Integrons are genetic recombination platforms that enhance bacterial evolvability by enabling the acquisition and differential expression of new genes. These genes are embedded in mobile elements, named cassettes, which can be stockpiled to form a long array of adaptive functions whose expression is driven by the Pc promoter within the integron platform. Integron recombination is governed by the integrase, a distinct type of tyrosine recombinase. This protein can integrate, excise, and reshuffle integron cassettes through different reactions between the attachment sites in the integron platform (attI) and those in cassettes (attC). These rearrangements can modulate the expression of genes by modifying their distance to the Pc promoter. Integrons are ancient structures found in the chromosomes of many bacterial species. Their activity is exquisitely intertwined with bacterial physiology through the coupling to the SOS response. These sedentary chromosomal integrons (SCIs) carry cassette arrays of functions that still nowadays remain broadly cryptic. The intensive use of antibiotics has selected for the transposon-mediated mobilization of integrons harboring antibiotic resistance genes onto conjugative elements. These so-called mobile integrons (MIs) have disseminated to many environmental niches and are currently prevalent in hospitals worldwide. MIs meant the arrival of bacterial multiresistance more than 50 years ago. Today, they represent a major threat to antibiotic chemotherapy and, consequently, to modern medicine. Recombination in integrons is unique. This is the consequence of the single-stranded nature of attC sites and the constraints that such substrates impose on the recombination process. Understanding these recombination reactions tells the evolutionary story of integrons, a tale of innovation that we are only starting to unveil.
This work was supported by the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS-UMR3525), the European Union Seventh Framework Program (FP7-HEALTH- 2011-single-stage), the “Evolution and Transfer of Antibiotic Resistance” (EvoTAR) project, the Fondation pour la Recherche Medicale (FRM) project DBF20160635736 and the French Government’s Investissement d’Avenir program Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62-IBEID), and the French National Research Agency (ANR-12-BLAN-DynamINT). JAE is supported by the Marie Curie Intra-European Fellowship for Career Development (FP-7-PEOPLE-2011-IEF, ICADIGE) and by the 2016-T1/BIO-1105 project of the Atracción de Talento Program of the Comunidad de Madrid.
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