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Updated: Jul 29, 2025

Quantification of Plasmid-Mediated Antibiotic Resistance in an Experimental Evolution Approach
Published on: December 14, 2019
Plasmid Costs Explain Plasmid Maintenance, Irrespective of the Nature of Compensatory Mutations
João S Rebelo1, Célia P F Domingues1,2, Francisco Dionisio1
1cE3c-Centre for Ecology, Evolution and Environmental Changes & CHANGE, Global Change and Sustainability Institute, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal.
Abstract:
Conjugative plasmids often carry virulence and antibiotic-resistant genes. Therefore, understanding the behavior of these extra-chromosomal DNA elements gives insights into their spread. Bacteria frequently replicate slower after plasmids' entry, an observation inconsistent with the plasmids' ubiquity in nature. Several hypotheses explain the maintenance of plasmids among bacterial communities. However, the numerous combinations of bacterial species and strains, plasmids, and environments claim a robust elucidatory mechanism of plasmid maintenance. Previous works have shown that donor cells already adapted to the plasmid may use the plasmid as a 'weapon' to compete with non-adapted plasmid-free cells. Computer simulations corroborated this hypothesis with a wide range of parameters. Here we show that donor cells benefit from harboring conjugative plasmids even if compensatory mutations in transconjugant cells occur in the plasmid, not on chromosomes. The advantage's leading causes are as follows: mutations take time to appear, many plasmids remain costly, and re-transfer of mutated plasmids usually occurs in sites distant to the original donors, implying little competition between these cells. Research in previous decades cautioned against uncritical acceptance of the hypothesis that resistance cost helps to preserve antibiotics' effectiveness. This work gives a new twist to this conclusion by showing that costs help antibiotic-resistant bacteria to compete with plasmid-free cells even if compensatory mutations appear in plasmids.
Insights
Conjugative plasmids, carrying antibiotic resistance genes, benefit bacteria by aiding competition against plasmid-free cells. This advantage persists even when mutations occur within the plasmid, highlighting plasmid maintenance strategies.
Area of Science:
- Microbiology
- Evolutionary Biology
- Genetics
Background:
- Conjugative plasmids frequently harbor virulence and antibiotic resistance genes, influencing bacterial evolution and spread.
- The ubiquity of plasmids despite a known replication cost suggests strong selective advantages for host bacteria.
- Existing hypotheses for plasmid maintenance do not fully account for the diverse interactions between bacteria, plasmids, and environments.
Purpose of the Study:
- To investigate the selective advantages conferred by conjugative plasmids to host bacteria, particularly under conditions where compensatory mutations arise.
- To elucidate the mechanisms maintaining plasmids in bacterial populations despite potential fitness costs.
Main Methods:
- Utilized computer simulations to model bacterial populations with and without conjugative plasmids under various conditions.
- Analyzed the impact of compensatory mutations occurring within plasmids versus chromosomal mutations on bacterial fitness and plasmid maintenance.
Main Results:
- Donor bacterial cells benefit from harboring conjugative plasmids, even when compensatory mutations occur within the plasmid.
- Key factors contributing to this advantage include the time required for mutations to appear, the inherent cost of many plasmids, and the spatial separation of re-transfer events.
- This challenges the notion that plasmid costs solely hinder antibiotic effectiveness, showing they can aid antibiotic-resistant bacteria's competitiveness.
Conclusions:
- Conjugative plasmids provide a competitive edge to bacteria, facilitating their persistence in populations.
- The study refines understanding of plasmid maintenance, emphasizing the role of mutation dynamics and spatial factors.
- Findings offer a new perspective on the interplay between antibiotic resistance, plasmid costs, and bacterial competition.
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