Coupled environmental and demographic fluctuations shape the evolution of cooperative antimicrobial resistance

TL;DR

This study explores how environmental and demographic fluctuations influence the evolution and coexistence of resistant and sensitive microbes, revealing mechanisms that could lead to eradicating antimicrobial resistance.

Contribution

It introduces a model combining environmental fluctuations and demographic noise to analyze antimicrobial resistance evolution, highlighting fluctuation-driven eradication mechanisms.

Findings

Environmental fluctuations can promote coexistence or fixation of resistant strains.

Bottlenecks caused by environmental changes can lead to resistant strain extinction.

Analytical and computational methods identify conditions for resistance eradication.

Abstract

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 behavior 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, modeled by a carrying capacity randomly switching between states of abundance and scarcity. We assume that antimicrobial resistance 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 a fluctuation-driven antimicrobial resistance eradication mechanism, where resistant microbes experience bottlenecks leading to extinction. We also discuss the possible applications of our findings to laboratory-controlled experiments.