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  resistance typically has a reproductive cost to the microbes, there can be trade-offs between resistance and competitiveness depending on the environment. Here we show conditions under which such trade-offs 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 the trade-offs between susceptibility and resistance when the antibiotic is applied or is not , 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.
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.
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competition can reduce fitness and
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to the microbes, there can be trade-offs between resistance and competitiveness depending on the
, resistant mutants' fitness can depend on their
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such trade-offs
environmental varying fitness
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the trade-offs between susceptibility and resistance when the antibiotic is applied or is not
competition