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Published on: September 16, 2022
The emergence, maintenance, and demise of diversity in a spatially variable antibiotic regime
1Department of Biology University of Ottawa Ottawa Ontario K1N 6N5 Canada.
Abstract:
Antimicrobial resistance (AMR) is a growing global threat that, in the absence of new antibiotics, requires effective management of existing drugs. Here, we use experimental evolution of the opportunistic human pathogen Pseudomonas aeruginosa to explore how changing patterns of drug delivery modulates the spread of resistance in a population. Resistance evolves readily under both temporal and spatial variation in drug delivery and fixes rapidly under temporal, but not spatial, variation. Resistant and sensitive genotypes coexist in spatially varying conditions due to a resistance-growth rate trade-off which, when coupled to dispersal, generates negative frequency-dependent selection and a quasi-protected polymorphism. Coexistence is ultimately lost, however, because resistant types with improved growth rates in the absence of drug spread through the population. These results suggest that spatially variable drug prescriptions can delay but not prevent the spread of resistance and provide a striking example of how the emergence and eventual demise of biodiversity is underpinned by evolving fitness trade-offs.
Insights
Antimicrobial resistance (AMR) spread can be delayed by spatially varying drug delivery, but not prevented. This occurs due to evolving trade-offs between resistance and growth rates in Pseudomonas aeruginosa populations.
Area of Science:
- Microbiology
- Evolutionary Biology
- Pharmacology
Background:
- Antimicrobial resistance (AMR) is a significant global health challenge.
- Effective management of existing antibiotics is crucial due to a lack of new drug development.
- Understanding how drug delivery impacts resistance evolution is vital.
Purpose of the Study:
- To investigate how varying drug delivery patterns influence the spread of antimicrobial resistance.
- To explore the evolutionary dynamics of resistance in Pseudomonas aeruginosa under different drug exposure scenarios.
Main Methods:
- Experimental evolution of Pseudomonas aeruginosa.
- Manipulation of temporal and spatial drug delivery patterns.
- Analysis of resistance evolution and genotype coexistence.
Main Results:
- Resistance readily evolves under both temporal and spatial drug variation.
- Resistance fixed rapidly under temporal variation but not spatial variation.
- Spatial variation allowed temporary coexistence of resistant and sensitive strains due to a resistance-growth trade-off.
- Coexistence was eventually lost as fitter resistant strains proliferated.
Conclusions:
- Spatially variable drug prescriptions can delay, but not ultimately prevent, the spread of antimicrobial resistance.
- Evolving fitness trade-offs drive the emergence and loss of biodiversity in microbial populations.
- This study provides insights into the complex interplay between drug exposure, evolution, and resistance dynamics.
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