Suppressing evolution through environmental switching

TL;DR

This paper investigates how environmental switching strategies, such as pulsed antibiotic application, can suppress microbial infections and prevent resistance emergence by exploiting competition and fitness costs.

Contribution

It introduces a stochastic Lotka-Volterra model to analyze how fluctuating environments can be used to control resistance development in microbial populations.

Findings

Environmental switching can suppress infections effectively.

Pulsed antibiotic strategies can prevent resistant mutants.

Competition reduces fitness of resistant strains under certain conditions.

Abstract

Ecology and evolution under changing environments are important in many subfields of biology with implications for medicine. Here, we explore an example: the consequences of fluctuating environments on the emergence of antibiotic resistance, which is an immense and growing problem. Typically, high doses of antibiotics are employed to eliminate the infection quickly and minimize the time under which resistance may emerge. However, this strategy may not be optimal. Since competition can reduce fitness and resistance typically has a reproductive cost, resistant mutants' fitness can depend on their environment. Here we show conditions under which environmental varying fitness can be exploited to prevent the emergence of resistance. We develop a stochastic Lotka-Volterra model of a microbial system with competing phenotypes: a wild strain susceptible to the antibiotic, and a mutant strain that is resistant. We investigate the impact of various pulsed applications of antibiotics on population suppression. Leveraging competition, we show how a strategy of environmental switching can suppress the infection while avoiding resistant mutants. We discuss limitations of the procedure depending on the microbe and pharmacodynamics and methods to ameliorate them.