I alternate therefore I generalize: how the intrinsic resistance risk of fungicides counterbalances their durability

The evolution of resistance to pesticides is a major burden in agriculture. Resistance management involves maximizing selection pressure heterogeneity, particularly by combining active ingredients with different modes of action. We tested the hypothesis that alternation may delay the build-up of resistance not only by spreading selection pressure over longer periods, but also by decreasing the rate of evolution of resistance to alternated fungicides, by applying an experimental evolution approach to the economically important crop pathogen Zymoseptoria tritici. Our results show that alternation is either neutral or slows the evolution of resistance, relative to continuous fungicide use, but results in higher levels of generalism in evolved lines. We demonstrate that the relative risk of resistance intrinsic to fungicide alternation probably underlies a trade-off between the number of fungicides and the frequency of alternation. This trade-off is also dynamic over the course of resistance evolution. These findings open up new possibilities for tailoring resistance management effectively while optimizing interplay between alternation components.