We have implemented a combination of experimental microbiology, experimental evolution, deep-sequencing based technique, comparative approaches and modelling and the main results are:
The main results of the action are:
- when antibiotic resistance genes move by horizontal transfer fom one species to another, the level of resistance they confer vary strongly. The factors determining the resistance levles are manyfold and include the carriage by mobile genetic elements, the adequation between the gene transferred and the expression machinery of the receiving genome (promoter strength, synonymous variation,...). This implies that horizontal transfer is not a mechanism providing excatly the same function to all potential receiver genomes and that the circulation of resistance genes is strongly dependent on a gene * genome * environment interaction.
- receiving one or several genes by horizontal transfer is not only providing new pieces and new function but also genertaing selection pressures which trigger genetic changes elsewhere in the genome. We have shown this at two very difference time scales by experimental evolution and by a comparative pan-genome approach.
- the propagation dynamics of hypermutators and their role in the evolution of antibiotic resistance is more complex than predicted by theoretical models and result from an interplay between the intensity of the stress generated by antibiotics, the rate of mutations producing hypermutators (with a role of transposable elements) and the clonal interference in the hypermutator fraction of the populations.
- at the european scale, dynamics of the prevalence of aminoglycoside resistance genes are explained more by international trade and migrations and by exchanges within ecosystems than by antibiotic consumption. This prompts for taking measures beyond the reduction of antibiotic consumption reduction, which is necessary but not sufficient to start finding solution to this world-wide public health problem.
- at the world-wide level, the circulation of aminoglycoside resistance genes by horizontal transfer are mainly driven by the ecological distance, the phylogenetic distance and the (dis)similarity in codon usage between donors and receivers. These traffic rules can however be strongly changed when the gene is carried by mobile genetic elements and in particular nested ones which seem to allow high distance transfers. We have also shwon on the aminoglycoside resistance model, that frequent donors of these resistance genes are soil bacteria (including aminoglycoside producers) and that pathogens are overrepresented in the frequent receivers.
These results have been presented in various conferences and workshops including the SMBE conference and the Evolutionary Medecine and Public Health conference. They have been published in five published papers and an online prepints and eight more papers are in preparation.
