Unbridled Integrons: A Matter of Host Factors

Abstract

Integrons are powerful recombination systems found in bacteria, which act as platforms capable of capturing, stockpiling, excising and reordering mobile elements called cassettes. These dynamic genetic machineries confer a very high potential of adaptation to their host and have quickly found themselves at the forefront of antibiotic resistance, allowing for the quick emergence of multi-resistant phenotypes in a wide range of bacterial species. Part of the success of the integron is explained by its ability to integrate various environmental and biological signals in order to allow the host to respond to these optimally. In this review, we highlight the substantial interconnectivity that exists between integrons and their hosts and its importance to face changing environments. We list the factors influencing the expression of the cassettes, the expression of the integrase, and the various recombination reactions catalyzed by the integrase. The combination of all these host factors allows for a very tight regulation of the system at the cost of a limited ability to spread by horizontal gene transfer and function in remotely related hosts. Hence, we underline the important consequences these factors have on the evolution of integrons. Indeed, we propose that sedentary chromosomal integrons that were less connected or connected via more universal factors are those that have been more successful upon mobilization in mobile genetic structures, in contrast to those that were connected to species-specific host factors. Thus, the level of specificity of the involved host factors network may have been decisive for the transition from chromosomal integrons to the mobile integrons, which are now widespread. As such, integrons represent a perfect example of the conflicting relationship between the ability to control a biological system and its potential for transferability.

Cassette recombination dynamics within chromosomal integrons are regulated by toxin–antitoxin systems

“…Therefore, the very stress that induces the expression of the integrase allows the screening for a set of cassettes that may in turn enable the cell to escape from it. For this reason, integrons are described as “on demand” adaptation systems [9,10].…”

“…Remarkably, we previously found that the integrase, which catalyze the cassette shuffling, is part of the SOS regulon 8 . For this reason, integrons are described as "on demand" adaptation systems 9,10 . The integron integrase (IntI) has a very singular place among the broad family of the tyrosine recombinases 11 .…”

“…While MIs can store up to 10 cassettes, SCIs can easily store dozens of them (up to 301 in Vibrio vulnificus ), encompassing a substantial fraction of their host genomes 3 . For this reason, it was argued that the high genetic capacitance of SCIs allows them to serve as cassette reservoir for MIs which can compile from it the most relevant cassette repertoire in a given environment 10,15 . However, it is not clear how such massive and silent structure as SCIs can be stabilized in bacterial genomes.…”

High Occurrence of Multiple-Drug Resistance Mediated by Integron in Aeromonas Isolated from Fish-Livestock Integrated Farms

“…Tese may have lost gene cassettes in the absence of antimicrobial selective pressure or on the other hand, never acquired the resistance gene insert [48]. However, they can acquire new resistance genes and facilitate the dissemination of resistance in bacteria [13].…”

“…Genetic elements, such as plasmids, transposons, and integrons, can be transferred horizontally between bacteria of diferent origins. Integrons are especially important among these genetic elements given their ability to capture and express resistance genes harbored by diferent gene cassettes [13]. Class 1 integrons, the most common integrons, have a complete structure containing a 5′-conserved segment, variable gene cassettes, and 3′-conserved segment.…”