Mobile Genetic Elements and Antimicrobial Resistance

Mobile genetic elements (MGEs) are discrete DNA units that facilitate the movement and rearrangement of genetic material within and between microbial genomes. Key MGE classes include plasmids, transposons, insertion sequences and integrons. These elements underpin horizontal gene transfer (HGT) through mechanisms such as conjugation, transduction and transformation, driving the rapid dissemination of antimicrobial resistance genes (ARGs) across diverse bacterial populations. Under antimicrobial selection pressure, MGEs not only mediate the initial capture of resistance determinants but also can promote gene amplification and duplication, enhancing resistance phenotypes. The global expansion of multidrug-resistant pathogens, in human, veterinary and environmental settings, reflects the interplay between antimicrobial use, MGE dynamics and microbial ecology. Advances in long-read sequencing and experimental evolution have revealed the structural diversity of resistance-carrying MGEs, providing insight into how environmental reservoirs and clinical strains exchange ARGs. Understanding MGE biology is thus critical for devising interventions that limit the spread of resistance, from molecular inhibitors of transposition to strategies that disrupt plasmid maintenance in pathogens.

Research from Nature Portfolio

Recent studies have demonstrated that antibiotic selection can drive the evolution of duplicated resistance genes via the transposition activities of MGEs. Modelling and experimental evolution, coupled with long-read sequencing of thousands of bacterial isolates, revealed that duplicated ARGs accumulate preferentially in environments associated with antibiotic exposure, such as human and livestock microbiomes. These duplicated genes often reside within transposase-mediated arrays, amplifying resistance under selective pressure. Another investigation focused on a multidrug-resistant Klebsiella pneumoniae clone, uncovering that IS26 units can form circular translocatable units (TUs) in both mono- and multimeric forms. Under antimicrobial selection, these TUs undergo tandem amplification and maintain their amplified state even when antibiotics are withdrawn. The study elucidated RecA-dependent and independent mechanisms governing TU formation and preservation, shedding light on the dynamic genome amplification that underlies persistent resistance in clinical strains.

Research from all publishers

Clinical surveillance of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae identified plasmid-encoded ESBL gene duplications in Escherichia coli and Klebsiella pneumoniae. These duplications, mediated by insertion sequence transposition, correlated with elevated ceftazidime minimum inhibitory concentrations, underscoring gene copy number as a determinant of resistance severity. Metagenomic analyses of mouse and cattle microbiomes have examined the association between insertion sequences and ARGs, revealing statistically significant correlations but highlighting challenges due to fragmented assemblies. The work emphasises the need for more complete long-read metagenomes to accurately map MGE-mediated ARG mobility within complex communities. In parallel, emerging antimicrobial strategies target the elimination of resistance plasmids, exploring chemical agents that destabilise plasmid replication and biological approaches such as plasmid-curing phages or CRISPR-based systems. These interventions aim to reduce the reservoir of ARG carriers in clinical and environmental settings, signalling a shift towards MGE-focused control measures in the fight against antimicrobial resistance.

Mobile Genetic Elements and Antimicrobial Resistance publication trend

The graph below shows the total number of articles in mobile genetic elements and antimicrobial resistance across all publications each year (not limited to Nature Index journals).

Technical terms

Mobile genetic element (MGE): A DNA segment capable of moving or being transferred within a genome or between organisms.

Horizontal gene transfer (HGT): The non-vertical acquisition of genetic material, enabling rapid trait dissemination.

Plasmid: Autonomous, usually circular, DNA molecule that replicates independently of the chromosome and often carries ARGs.

Transposon: A composite DNA element that moves within genomes, typically carrying one or more genes such as ARGs.

Insertion sequence (IS): A simple transposable element encoding only the proteins required for its own mobility.

Integron: A genetic platform that captures and expresses gene cassettes, frequently including resistance determinants.

Translocatable unit (TU): A circular DNA intermediate consisting of an insertion sequence and adjacent DNA, capable of reintegration.

References

1. Duplicated antibiotic resistance genes reveal ongoing selection and horizontal gene transfer in bacteria. Nature Communications (2024).
2. Generation and maintenance of the circularized multimeric IS26-associated translocatable unit encoding multidrug resistance. Communications Biology (2024).
3. Plasmid-encoded gene duplications of extended-spectrum β-lactamases in clinical bacterial isolates. Frontiers in Cellular and Infection Microbiology (2024).
4. Studying the Association between Antibiotic Resistance Genes and Insertion Sequences in Metagenomes: Challenges and Pitfalls. Antibiotics (2023).
5. Targeting Plasmids to Limit Acquisition and Transmission of Antimicrobial Resistance. Frontiers in Microbiology (2020).