Cost of resistance: an unreasonably expensive concept

Abstract

The cost of resistance, or the fitness effect of resistance mutation in absence of the drug, is a very widepsread concept in evolutionary genetics and beyond. It has represented an important addition to the simplistic view that resistance mutations should solely be considered as beneficial mutations. Yet, this concept also entails a series of serious difficulties in its definition, interpretation and current usage. In many cases, it may be simpler, clearer, and more insightful to study, measure and analyze the fitness effects of mutations across environments and to better distinguish those effects from 'pleiotropic effects' of those mutations.

Insecticide resistance and fitness cost in Bemisia tabaci (Hemiptera: Aleyrodidae) invasive and resident species in La Réunion Island

“…8 An absence of fitness cost may be due to favourable rearing conditions in the laboratory, failing to reveal costs that would be measurable under more stressful conditions. 7 Despite potential experimental limitations, our results are in line with Basit et al, who found no detrimental impact of the resistance to acetamiprid when comparing susceptible populations to an acetamiprid-selected population. 71 Likewise, in the MEAM1 species, resistance to pyriproxyfen was not associated with fitness cost.…”

“…It should be noted that experiments on fitness cost measured in the laboratory cannot predict the effective fitness cost in the natural environment . An absence of fitness cost may be due to favourable rearing conditions in the laboratory, failing to reveal costs that would be measurable under more stressful conditions . Despite potential experimental limitations, our results are in line with Basit et al ., who found no detrimental impact of the resistance to acetamiprid when comparing susceptible populations to an acetamiprid‐selected population .…”

“…While resistance to insecticide confers an obvious advantage in treated environments, it may be counterselected in the absence of treatment . The potential lower fitness of individuals carrying resistant alleles in the absence of insecticide is considered as a resistance cost . Such costs are due to the (near) loss of function in genes that are essential for viability or to the reallocation of resources and energy to resistance mechanisms instead of other fitness‐enhancing traits .…”

“…6 The potential lower fitness of individuals carrying resistant alleles in the absence of insecticide is considered as a resistance cost. 7 Such costs are due to the (near) loss of function in genes that are essential for viability or to the reallocation of resources and energy to resistance mechanisms instead of other fitness-enhancing traits. 6 If fitness costs associated with resistance are high, resistant individuals can be counterselected in the absence of treatments, resulting in delayed diffusion and fixation of resistant genotypes.…”

Turnover modulates the need for a cost of resistance in adaptive therapy

“…"Cost of resistance" means that a resistance adaptation confers a fitness advantage under drug exposure, but it comes at a fitness cost in a treatment-free environment [2,15]. It is a phenomenon which has been widely studied in agricultural pests and antibiotic resistance [16,17] and is typically experimentally measured in one of three ways: i) Mono-culture experiments, which measure the growth rate of the resistant population in the absence of drug in isolation, ii) Competition experiments, which study the relative frequency of sensitive and resistant cells over time when cultured together, and iii) Reversal experiments, which explore how long it takes for resistant cells to lose their resistance mechanism if grown in the absence of drug ( Figure 1A-C).…”