An analysis of the evolutionary relationships of integron integrases, with emphasis on the prevalence of class 1 integrons in Escherichia coli isolates from clinical and environmental origins.

Integrons are genetic elements that allow the mobilization and expression of smaller elements called gene cassettes, and are considered to be key elements in the evolution of antibiotic resistance among enteric bacteria. Although in nature integrons appear to be abundant, the presence of class 1 integrons in Escherichia coli has been reported to be much less frequent among isolates of non-human origin than among clinical ones. Searching for integrons in a wide variety of E. coli isolates we found a steep decline in class 1 integron prevalence when going from clinical strains to environmental ones, from outdoor urban dust to the microbiota of wild animals. Attempting to assess the causes of this decline, we addressed the evolution of integron integrases, comparing the amino acid sequence of various of these enzymes, the key proteins in gene-cassette mobilization. We found that all integrases are homologues, but different classes have been recruited by enteric bacteria, supporting the notion that integrons can frequently be gained and lost. Additionally, we found that phylogenetically distant organisms that bear intI1, such as E. coli and other enteric bacteria, but also the Gram-positive corynebacteria, have a similar preferential genomic codon usage (CU), suggesting that CU might play an important role in the acquisition and/or maintenance of integrons. In fact, the CU of intI1 is more similar to the preferential genomic CU of non-enteric bacteria than it is to that of E. coli. CU has been proposed to be involved in the retention of horizontally transferred genes; integrons in E. coli are often plasmid-borne. This might explain the reduced prevalence of integrons in enteric bacteria when not under the selective pressure of antibiotics. Collectively, our results provide evidence that class 1 integrons are important gene mobilizers within E. coli, but are not acquired and/or stably maintained without selective pressure. Thus, although not effective to reduce the prevalence of resistance itself, decreasing the use of antibiotics could be useful to diminish the presence of gene-mobilization machineries.