Documentation

The Importance of Transposable Elements

Transposable elements (TE) are key facilitators of bacterial adaptation and therefore are central players in the emergence of multiple antibacterial resistances such as resistance to antibiotics, heavy metals and to transmission of pathogenic traits. TE capture passenger genes using a number of mechanisms and transmit them to larger mobile genetic elements, plasmids, where they accumulate and are then transferred within and between bacterial populations. TE also contribute significantly to the ongoing reorganization of bacterial genomes, giving rise to new strains that are more and more adept at proliferating both in the environment and in hospitals. Understanding TE nature, distribution and action is therefore an indispensable part of the struggle to cope with the public health crisis of multiple antimicrobial resistance (AMR) (1,2). To understand the impact of TE on bacterial populations, to follow the flow of genes important in public health both in clinical and environmental settings and to provide some measure of understanding which might allow prediction of resistance transmission, it is essential to provide a detailed description and catalog of TE structures and diversity. This has already been undertaken for the simplest TE, the insertion sequences (IS), in the form of the online knowledge base ISfinder (https://www-is.biotoul.fr/index.php) (3,4), an international resource for IS currently including over 5000 individual examples. The ISfinder platform also includes a set of software tools, ISsaga, allowing semi-automatic genome annotation for IS using the ISfinder database (5). Although movement of IS has a profound and continuous impact on genome organization and function due to their ability to rearrange DNA, regulate neighboring genes and generate mutations (6–9), they do not themselves generally carry integrated passenger genes.

There are a large number of significantly more complex TE, arguably even more important in the global emergence of AMR. These are generically called transposons and may carry multiple passenger genes, including some of the most clinically important antibiotic resistance genes. They are grouped into a number of distinct families with characteristic organizations (6). Like IS, their transposition activities facilitate the rapid spread of groups of antibiotic resistance genes and promote their horizontal transfer to other bacterial strains, species and genera via natural vectors such as conjugal plasmids and bacterial viruses. Yet another important aspect of their impact is their ability to assemble passenger genes into resistance clusters (10,11). While there appears to be wide-spread appreciation that mobile plasmids are responsible for the spread of antibiotic resistance, fewer people are aware that IS and transposons are the conduit that transfers this information between chromosomes and plasmids.

It is crucial to stress the importance of educating the clinical world concerning transposition mechanisms in an easy-to-use way. Most scientists consider that IS/Tn all behave in the same way and believe that cataloging them is simply “busy-work”. However, a thorough understanding of how IS/Tn assemble antimicrobial resistance genes and effect rapid changes in plasmid vector structure is critical to understanding the increasingly efficient AMR spread observed today and combatting future AMR outbreaks (see Figure 1).