The evolutionary significance of synonymous variations: can codon usage preferences drive the propagation of antibiotic resistance?
The intensive use of antibiotics provided an unprecedented improvement in infectious disease treatments but at the expense of creating ideal conditions for the selection of widespread resistance. Propagation of antibiotic resistances is favoured by horizontal gene transfer and by bacterial life in multispecies community. However, compositions of resistome and bacterial communities are often correlated, suggesting that propagation of resistances does not occur at random. This project will test the hypothesis that mismatch in codon preferences between the transferred genes and the receiving genome is a fundamental factor shaping resistome structure and evolution. Such central role of codon preferences may have been hitherto overlooked. The project combines mutant collection characterization, experimental evolution approaches –one in a multispecies context and one in a variable environment context-, full genome sequencing of evolved populations, phylogenomics and mathematical modelling integrating the experimental results of the other approaches, and generating a predictive tool about the evolutionary outcome of various real-life situations.