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Updated: Dec 20, 2025
Quantification of Plasmid-Mediated Antibiotic Resistance in an Experimental Evolution Approach
Published on: December 14, 2019
Simulating the Influence of Conjugative-Plasmid Kinetic Values on the Multilevel Dynamics of Antimicrobial Resistance
Marcelino Campos1,2, Álvaro San Millán1,3,4, José M Sempere2
1Department of Microbiology, Ramón y Cajal University Hospital, IRYCIS, Madrid, Spain.
Abstract:
Bacterial plasmids harboring antibiotic resistance genes are critical in the spread of antibiotic resistance. It is known that plasmids differ in their kinetic values, i.e., conjugation rate, segregation rate by copy number incompatibility with related plasmids, and rate of stochastic loss during replication. They also differ in cost to the cell in terms of reducing fitness and in the frequency of compensatory mutations compensating plasmid cost. However, we do not know how variation in these values influences the success of a plasmid and its resistance genes in complex ecosystems, such as the microbiota. Genes are in plasmids, plasmids are in cells, and cells are in bacterial populations and microbiotas, which are inside hosts, and hosts are in human communities at the hospital or the community under various levels of cross-colonization and antibiotic exposure. Differences in plasmid kinetics might have consequences on the global spread of antibiotic resistance. New membrane computing methods help to predict these consequences. In our simulation, conjugation frequency of at least 10-3 influences the dominance of a strain with a resistance plasmid. Coexistence of different antibiotic resistances occurs if host strains can maintain two copies of similar plasmids. Plasmid loss rates of 10-4 or 10-5 or plasmid fitness costs of ≥0.06 favor plasmids located in the most abundant species. The beneficial effect of compensatory mutations for plasmid fitness cost is proportional to this cost at high mutation frequencies (10-3 to 10-5). The results of this computational model clearly show how changes in plasmid kinetics can modify the entire population ecology of antibiotic resistance in the hospital setting.
Insights
Bacterial plasmids carrying antibiotic resistance genes spread rapidly. Understanding plasmid kinetics, like conjugation and loss rates, is key to predicting antibiotic resistance dynamics in complex environments such as hospitals.
Area of Science:
- Microbiology
- Computational Biology
- Evolutionary Biology
Background:
- Bacterial plasmids carrying antibiotic resistance genes are major drivers of antibiotic resistance.
- Plasmids vary in kinetic properties (conjugation, segregation, loss rates), cellular fitness costs, and compensatory mutation frequencies.
- The impact of these kinetic variations on plasmid success in complex ecosystems like the microbiota remains unclear.
Purpose of the Study:
- To investigate how variations in plasmid kinetic values influence the ecological success of antibiotic resistance genes within bacterial populations.
- To predict the consequences of plasmid kinetic differences on the global spread of antibiotic resistance, particularly in hospital settings.
Main Methods:
- Utilized membrane computing methods for computational modeling.
- Simulated bacterial populations and plasmid dynamics under various conditions.
Main Results:
- Conjugation frequency ≥10⁻³ promotes the dominance of strains with resistance plasmids.
- Coexistence of multiple antibiotic resistances is facilitated by host strains maintaining two similar plasmids.
- Low plasmid loss rates (10⁻⁴–10⁻⁵) or high fitness costs (≥0.06) favor plasmids in abundant species.
- Compensatory mutations enhance plasmid fitness proportionally to the cost at high mutation rates (10⁻³–10⁻⁵).
Conclusions:
- Plasmid kinetics significantly impact the population ecology of antibiotic resistance.
- Computational models can predict how changes in plasmid characteristics alter resistance spread in environments like hospitals.
