Abstract
In front of the antibiotic pressure, a wide range of resistance mechanisms exist. They represent an increasing public health issue, which does and will have major consequences on human mortality. Current strategies —mostly based on antibiotic consumption reductions— globally fail to contain this persistent issue. Moreover, even though it is undeniable that the extensive antibiotic use during the past decades has been a driver of antibiotic resistance evolution, its impact on the emergence and the propagation of antibiotic resistance is often overestimated compared to other factors. First, selection on antibiotic resistance cannot be restricted to the medical and veterinary uses of antibiotics. Second, the evolution (i.e. the emergence, maintenance and spread) of a trait in populations also relies on other evolutionary forces and ecological processes. Finally, the intertwining of these factors induces an intricate evolution of resistant phenotypes, relying on several scales ranging from genetic determinism to environmental dynamics. The aim of this thesis is therefore, through an eco-evolutionary approach, to improve the understanding of forces and mechanisms shaping directions and movements of antibiotic resistance genes. To do so, this thesis focuses on aminoglycoside resistance by modifying enzymes. The results of this work highlight the importance of ecological and genomic factors in the circulation of resistance genes, and thus conclude that integrative studies of resistance are thus required. To begin with, this thesis reveals that the distribution of aminoglycoside resistance is loosely linked to variation in aminoglycoside consumption across Europe, but strongly structured by globalization (trade, migration) and even more by ecological connectivity. Subsequent analysis underscores the underestimated role of non-pathogenic bacteria in the horizontal transfer of antibiotic resistance genes at large phylogenetic scales. In the light of these results, this thesis opens up a course of reflection on the study and management of antibiotic resistance.