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Updated: Mar 15, 2026
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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
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Plasmids promote antimicrobial resistance through insertion sequence-mediated gene inactivation.
Jorge Sastre-Dominguez1,2, Paloma Rodera-Fernandez1,2, Javier DelaFuente1
1Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain.
Nature Microbiology
|March 14, 2026
Summary
Plasmids carrying insertion sequences (IS) accelerate antimicrobial resistance (AMR) in bacteria by inactivating genes. This study reveals that plasmids promote AMR not just by spreading resistance genes, but also through IS-mediated gene disruption.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Plasmids are key drivers of antimicrobial resistance (AMR) gene dissemination in bacterial populations.
- Insertion sequences (IS) are mobile genetic elements that can transpose within genomes and plasmids.
- IS elements on plasmids can potentially contribute to AMR evolution through gene disruption.
Purpose of the Study:
- To investigate the role of plasmids in promoting AMR via IS-mediated gene inactivation.
- To determine if plasmid-encoded IS elements increase the rate of antibiotic resistance acquisition.
- To explore the prevalence and mechanisms of IS-mediated gene inactivation in AMR evolution.
Main Methods:
- Combined experimental, bioinformatic, and computational approaches.
- Utilized plasmid pOXA-48 encoding IS1 elements in Klebsiella pneumoniae.
- Screened genome databases for plasmid-encoded IS elements and gene inactivation events.
- Developed a computational model to simulate AMR acquisition in bacterial communities.
Main Results:
- Plasmid pOXA-48 significantly increased the rate of multi-antibiotic resistance acquisition in Klebsiella pneumoniae through IS1-mediated gene disruption.
- Genome database screening confirmed IS-mediated gene inactivation as a widespread mechanism in AMR evolution.
- Conjugative plasmids were shown to facilitate this AMR acquisition route within complex bacterial communities.
Conclusions:
- Conjugative plasmids contribute to AMR evolution through both resistance gene dissemination and IS-mediated gene inactivation.
- IS-mediated gene disruption by plasmid-encoded IS elements is a significant, previously underappreciated, mechanism of AMR acquisition.
- Understanding these mechanisms is crucial for combating the spread of antimicrobial resistance in clinical settings.
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