Preventing multiple resistance above all: new insights for managing fungal adaptation

Abstract

Sustainable crop protection is crucial for food security, but is threatened by the adaptation of diverse, evolving pathogen population. Resistance can be managed by maximizing selection pressure diversity, by dose variation and the spatial and temporal combination of active ingredients. We explored the interplay between operational drivers for maximizing management strategy sustainability relative to the resistance status of fungal populations. We applied an experimental evolution approach to three artificial populations of an economically important wheat pathogen, Zymoseptoria tritici, differing in initial resistance status. We revealed that diversified selection pressure limited the selection of resistance in naive populations and those with low frequencies of single. Increasing the number of modes of action delayed resistance development most effectively -- ahead of increasing the number of fungicides, fungicide choice based on resistance risk and temporal variation in fungicide exposure -- but favored generalism in the evolved populations. However, the prior presence of multiple resistant resistant isolates and their subsequent selection in populations overrode the effects of diversity in management strategies, incidentally invalidating any universal ranking. Initial resistance composition must therefore be considered specifically in sustainable resistance management, to address real-world field situation. Abbreviated summaryExperimental evolution is a relevant tool for exploring the determinants of antifungal adaptation in fungi. Here, using the model species Z. tritici and two fungicidal modes of action associated with contrasting resistance risks, we have demonstrated that initial population composition, and in particular the presence of multiple resistance, represents the main determinant of adaptive trajectories. Originality-Significance StatementPesticides are part of microbe environment in agricultural systems and may select for resistance. This adaptation of pathogens is a burden for plant health. Using an original multicriteria assessment and experimental evolution, we revealed that multi-fungicide use, selecting for multiple resistance, trumped any other driver of selection, invalidating any universal ranking of management strategies, a dispute extensively illustrated in literature and still inconclusive, especially in agriculture. This outcome refocuses the debate on population diversity and evolution rather than on the intrinsic properties of strategies, as mostly acclaimed in literature. From a practical point of view, our results highlight the importance of considering local population composition when recommending spraying programs. This practice is currently not generalized in agriculture but may be timely to effectively delay resistance evolution and reduce pesticide load in agricultural systems, a growing social demand, since resistance monitoring at relatively fine spatial scales and at low frequency may become commonplace in a near future with the rise of new molecular biology technologies