Cost of resistance: an unreasonably expensive concept

Abstract

The concept of “cost of resistance” has been very important for decades, for fundamental reasons (theory of adaptation), with a wide range of applications for the genetics and genomics of resistance: resistance to antibiotics, insecticide, herbicide, fungicides; resistance to chemotherapy in cancer research; coevolution between all kinds of parasites and their hosts. This paper reviews this history, including latest developments, shows the interest of the idea but also challenges the usefulness and limits of this widely used concept, based on the most recent development of adaptation theory. It explains how the concept can be flawed and how this can impede research efforts in the field of resistance at large, including all applied aspects. In particular, it would be clearer to simply measure the fitness effects of mutations across environments and to better distinguish those effects from ‘pleiotropic effects’ of those mutations. Overall, we show how to correct the concept, and how this correction helps to better understand the wealth of data that has accumulated in recent years. The main points are: 1. The concept of «cost of resistance» needs to be carefully used, to avoid misconceptions, false paradox and flawed applications. The recent developments in adaptation theory are useful to clarify this. 2. “Cost of resistance” and pleiotropy have to be distinguished. More than one trait is required to discuss pleiotropy. Resistance evolution must at least involve the modification of one trait. If there is an irreducible trade-off on that trait between environments with and without drug, it creates a fitness effect that is not due to pleiotropy. Pleiotropic effects can, but need not, occur in addition. 3. “Cost of resistance” must depend on the pair of environments considered with and without drug. Hence, there are as many measures of cost as there are environments without drug. If the focal genotype is not well adapted to one focal environment, it is relatively easy to observe “negative” costs of resistance. There is nothing surprising about this, and it does not indicate an absence of trade-off. 4. Environments with drug can differ according to the dose. It may be more informative to measure the possible trade-offs among all doses than to focus exclusively on the fitness contrast between the presence and the absence of drug.

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

“…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 .…”

Fitness of Herbicide-Resistant Weeds: Current Knowledge and Implications for Management

“…Herbicide resistance is an adaptive evolutionary process in response to new environmental conditions (i.e., weed chemical control) in the agroecosystem. Herbicide resistance alleles are beneficial mutations that rapidly spread in weed populations under recurrent herbicide exposure [15,16]. These resistance mutations establish diverse defence mechanisms that protect plants from herbicide damage in different ways [11,17].…”

Genetics and mechanisms of insecticide resistance in Ceratitis capitata and its implications for resistance management

“…Nonetheless, we have recently demonstrated that resistance to lambda-cyhalothrin in field populations was reverted by PBO (unpublished results), as reported for the laboratory selected strain (Arouri et al, 2015;Chapter 3). Apart from differences in the mechanism, the inheritance and fitness costs of resistance can also vary between laboratory and field environments (Ffrench-Constant and Bass, 2017;Lenormand et al, 2018). Ideally, resistant strains should be field derived and the costs and inheritance of resistance should be studied in the field.…”

“…However, it is relevant to outline that fitness cost observed in resistant laboratory strains is not necessarily the same that in field resistant populations. Indeed, care should be taken when extrapolating laboratory results to field populations because their environmental conditions and genetic backgrounds are not comparable, and field genotypes are not always wellknown (Ffrench-Constant and Bass, 2017;Lenormand et al, 2018). Our simulations showed that a considerable reduction in fitness cost would be required to result in an increase of resistant alleles in the population.…”