Abstract

Integrons are powerful bacterial genetic elements that permit the expression and dissemination of antibiotic-resistance gene cassettes. They contain a promoter Pc that allows the expression of gene cassettes captured through site-specific recombination catalyzed by IntI, the integron-encoded integrase. Class 1 and 2 integrons are found in both clinical and environmental settings. The regulation of intI and of Pc promoters has been extensively studied in class 1 integrons and the regulatory role of the SOS response on intI expression has been shown. Here we investigated class 2 integrons. We characterized the PintI2 promoter and showed that intI2 expression is not regulated via the SOS response. We also showed that, unlike class 1 integrons, class 2 integrons possess not one but two active Pc promoters that are located within the attI2 region that seem to contribute equally to gene cassette expression. Class 2 integrons mostly encode an inactive truncated integrase, but the rare class 2 integrons that encode an active integrase are associated with less efficient Pc2 promoter variants. We propose an evolutionary model for class 2 integrons in which the absence of repression of the integrase gene expression led to mutations resulting in either inactive integrase or Pc variants of weaker activity, thereby reducing the potential fitness cost of these integrons.

Highlights

  • Integrons are widely used by Gram-negative bacteria to resist antibiotics

  • The integron functional platform is composed of a gene that encodes a site-specific recombinase (IntI); a recombination site; and a functional promoter (Pc), divergently oriented to the integrase gene, that allows the expression of gene cassettes (Stokes and Hall, 1989)

  • We found that two promoters, Pc2A and Pc2B, seem to contribute to the expression of gene cassettes in class 2 integrons

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Summary

Introduction

Integrons are widely used by Gram-negative bacteria to resist antibiotics. These DNA elements can acquire, exchange and express promoterless coding sequences embedded within gene cassettes (Escudero et al, 2015). The integron functional platform is composed of a gene (intI) that encodes a site-specific recombinase (IntI); a recombination site (attI); and a functional promoter (Pc), divergently oriented to the integrase gene, that allows the expression of gene cassettes (Stokes and Hall, 1989). IntI catalyzes recombination events that lead either to the incorporation of gene cassettes within the integron, or to their excision. Several integron classes can be discriminated on the basis of their IntI sequences (Collis et al, 2002). Five integron classes involved in the expression and dissemination of antibiotic-resistance gene cassettes have been described. Class 1 integrons prevail in most epidemiological studies in human and animals, followed by class 2 integrons (Gillings, 2014)

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