The Natural History of Integrons

Abstract

Integrons were first identified because of their central role in assembling and disseminating antibiotic resistance genes in commensal and pathogenic bacteria. However, these clinically relevant integrons represent only a small proportion of integron diversity. Integrons are now known to be ancient genetic elements that are hotspots for genomic diversity, helping to generate adaptive phenotypes. This perspective examines the diversity, functions, and activities of integrons within both natural and clinical environments. We show how the fundamental properties of integrons exquisitely pre-adapted them to respond to the selection pressures imposed by the human use of antimicrobial compounds. We then follow the extraordinary increase in abundance of one class of integrons (class 1) that has resulted from its acquisition by multiple mobile genetic elements, and subsequent colonisation of diverse bacterial species, and a wide range of animal hosts. Consequently, this class of integrons has become a significant pollutant in its own right, to the extent that it can now be detected in most ecosystems. As human activities continue to drive environmental instability, integrons will likely continue to play key roles in bacterial adaptation in both natural and clinical settings. Understanding the ecological and evolutionary dynamics of integrons can help us predict and shape these outcomes that have direct relevance to human and ecosystem health.

Discovery of integrons in Archaea: platforms for cross-domain gene transfer

“…However, the molecular mechanisms underlying the integration of exogenous genes from foreign domains are mostly unknown. Integrons are a family of genetic elements that facilitate this process within Bacteria via site-specific DNA recombination [4][5][6][7] . Integrons, however, have not been reported outside Bacteria, and thus their potential role in cross-domain gene transfer has not been investigated.…”

“…Out of those with functional predictions, proteins involved in toxin-antitoxin (TA) systems (10.5%); phage resistance proteins via DNA methylation or restriction endonuclease activities (8.3%); and acetyltransferases (4.4%) were particularly prevalent (Supplementary Table 5). These are the functions most commonly reported for gene cassettes in Bacteria 5,7,33,34,40 . TA gene cassettes are particularly common in bacterial integrons, where they can stabilise very large cassette arrays 41,42 .…”

“…Signal peptides are short amino acid tag sequences that target proteins into, or across, membranes. Again, transmembrane and secreted proteins are commonly encoded by gene cassettes in Bacteria 33 , and are hypothesised to help facilitate interactions with their broader environment 7 .…”

Methods for the targeted sequencing and analysis of integrons and their gene cassettes from complex microbial communities

“…Gene cassettes have been found to be extraordinarily abundant and diverse in every environment surveyed [20][21][22][23][24][25][26]. Further, many cassettes with known functions act as single-gene/single-trait entities [17,27]. As such, they need minimal integration into metabolic networks and can likely function in a relatively wide range of genomic contexts.…”

Carriage of antibiotic resistant bacteria in endangered and declining Australian pinniped pups

“…The class 1 integron contains a conserved 5' segment which encodes the integrase gene (intI1) and a varying number of gene cassettes that together form a gene cassette array [15]. The conserved intI1 is a useful genetic indicator of antimicrobial pollution as it is universally present, occurs in high abundance in humans and domestic animals, is highly abundant in waste streams and is rarely present in environments less affected by humans [16,17]. The recombination of gene cassettes is mediated by intI1, allowing the class 1 integron to capture, remove and express a variety of gene cassettes [15].…”