Evolution of Integrons and Evolution of Antibiotic Resistance

Integrons were only formally identified as agents of antibiotic resistance gene recruitment in the late 1980s following the observation that transposons and R-plasmids expressing different antibiotic resistance phenotypes shared the same genetic backbone and differed only in the resistance genes they harbored. Integrons can be divided into two distinct subsets, the mobile integrons (MIs), linked to mobile DNA elements and primarily involved in the spread of antibiotic-resistance genes, and the superintegrons (SIs). Integrons are undoubtedly ancient entities, as indicated by the species-specific clustering of the respective SI integrase genes in a pattern that adheres, in several cases, to the line of descent among the bacterial species in which they are located. Thus, the establishment of SIs likely predates speciation within the respective genera, indicating that integrons are ancient structures that have been impacting on the evolution of bacterial genomes for hundreds of millions of years. The determination of the diverse number of metabolic activities associated with SI cassettes (other than antibiotic resistance and virulence) indicates that integrons operate as a general gene capture system in bacterial adaptation. Integrases encoded by integrons mediate recombination involving two types of sites-their specific attI site and the cassette-associated attC site-and are able to recombine distantly related DNA sequences. With the discovery of SIs, and of the thousands of gene cassettes associated with integrons that are located in the genomes of environmental bacterial species, the importance of these elements clearly extends beyond the phenomenon of antibiotic resistance.