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Abstract Antimicrobial resistance to drugs (AMR), a global threat to human and animal health, is often regarded as resulting from cooperative behaviour. Moreover, microbes generally evolve in volatile environments that, together with demographic fluctuations (birth and death events), drastically alter population size and strain survival. Motivated by the need to better understand the evolution of AMR, we study a population of time-varying size consisting of two competing strains, one drug-resistant and one drug-sensitive, subject to demographic and environmental variability. This is modelled by a binary carrying capacity randomly switching between mild and harsh environmental conditions, and driving the fluctuating volume (total amount of nutrients and antimicrobials at fixed concentration), and thus the size of the community (number of resistant and sensitive cells). We assume that AMR is a shared public good when the concentration of resistant cells exceeds a fixedconcentration cooperation threshold, above which the sensitive strain has a growth advantage, whereas resistant cells dominate below it. Using computational means, and devising an analytical treatment (built on suitable quenched and annealed averaging procedures), we fully characterise the influence of fluctuations on the eco-evolutionary dynamics of AMR, and notably obtain specific strain fixation and long-lasting coexistence probabilities as a function of the environmental variation rate and cooperation threshold. We find that microbial strains tend to coexistence, but demographic fluctuations eventually lead to the extinction of resistant or sensitive cells for small or large values of the concentration cooperation threshold, respectively. This also holds for dynamic environments, whose specific properties determine the extinction timescale.
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Coupled environmental and demographic fluctuations shape the evolution of cooperative antimicrobial resistance
There is a pressing need to better understand how microbial populations respond to antimicrobial drugs, and to find mechanisms to possibly eradicate antimicrobial-resistant cells. The inactivation of antimicrobials by resistant microbes can often be viewed as a cooperative behaviour leading to the coexistence of resistant and sensitive cells in large populations and static environments. This picture is, however, greatly altered by the fluctuations arising in volatile environments, in which microbial communities commonly evolve. Here, we study the eco-evolutionary dynamics of a population consisting of an antimicrobial-resistant strain and microbes sensitive to antimicrobial drugs in a time-fluctuating environment, modelled by a carrying capacity randomly switching between states of abundance and scarcity. We assume that antimicrobial resistance (AMR) is a shared public good when the number of resistant cells exceeds a certain threshold. Eco-evolutionary dynamics is thus characterised by demographic noise (birth and death events) coupled to environmental fluctuations which can cause population bottlenecks. By combining analytical and computational means, we determine the environmental conditions for the long-lived coexistence and fixation of both strains, and characterise afluctuation-drivenAMR eradication mechanism, where resistant microbes experience bottlenecks leading to extinction. We also discuss the possible applications of our findings to laboratory-controlled experiments.
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- Award ID(s):
- 2128587
- PAR ID:
- 10505698
- Publisher / Repository:
- The Royal Society Publ.
- Date Published:
- Journal Name:
- Journal of The Royal Society Interface
- Volume:
- 20
- Issue:
- 208
- ISSN:
- 1742-5662
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1098/rsif.2023.0393
