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Invited speakers
Stéphanie BEDHOMME Website Centre d'Écologie Fonctionnelle et Évolutive, UMR 5175, Montpellier
Talk "Following evolution after the horizontal transfer of synonymous versions of an antibiotic resistance gene". Horizontal gene transfer is a powerful mechanism by which antibiotic resistance spread among species.Despite this evolutionary success, there are a number of obstacles and mechanistic costs to the physical transfer and the maintenance of horizontally transferred genes.Here, I will focus on one of these mechanisms: transferred genes usually have codon preferences that differ from the ones of the receiving genome. This leads to translation errors, low translation rates and finally to low activity of the transferred gene and energetic costs for the receiving cell. It is thus predicted that (1) a gene with strong codon usage mismatch will generate a cost for the receiving cell and (2) its maintenance in the genome will trigger evolutionary changes both within and outside the transferred gene. To test these predictions, three synonymous versions of the Chloramphenicol Acetyl Transferase with different codon preferences were transformed in Escherichia coli. We verified that the mismatch in codon usage induced a fitness cost. This cost was compensated during experimental evolution in presence of chloramphenicol and this compensation was associated to a diversity of genomic changes including changes in the regulation of the translation of the transferred gene, large duplications, mutators, point mutations in global regulators... Temporal analysis revealed the importance of clonal and plasmid interference in the post-HGT evolutionary dynamics. Finally, horizontal transfer of antibiotic resistance gene reveals itself, not only as a spreading highway for these genes but also as a powerful mechanism pushing bacteria to explore new ways of functioning.
Research interests Stéphanie Bedhomme currently works on the evolutionary consequences of horizontal gene transfer. Horizontal gene transfer is a key mechanism in prokaryote genome evolution and more recently evidences have accumulated that point to its important role also in eukaryote genome evolution. Its evolutionary impact has been studied until now in terms of new functions and new properties provided by the acquired gene: colonization of new niches, acquisition of virulence factros modifying host-pathogen interactions… However, the insertion in a genome of an heterologous gene can also trigger selection pressures linked to the fact that horizontal gene transfer breaks gene-genome coadaptation. Indeed, a genome is characterized by its codon usage preferences, which reflects a coadaptation between the genome and the translation machinery. Her team has recently demonstrated in Escherichia coli that the introduction of an antibiotic resistance gene with maladapted codon usage preferences provides only a very partial antibiotic resistance. However, this cost can be compensated rapidly by mutations occurring in the promoter of the introduced gene and in different parts of the genome.
Hervé BLOTTIÈRE Website Institut Micalis, UMR1319, INRA, AgroParisTech, Jouy-en-Josas
Talk "Human Intestinal Microbiota and Health: from structure to functions" Our conception of human physiology has progressed a lot over the latest years, since the acknowledgment of the important role played by our microbiome. The intestinal microbiota is of great complexity, composed mostly of bacteria not yet cultivated. The metagenomic approach has allowed rapid advancement in characterizing the genetic and genomic diversity of our microbiota. The exhaustive sequencing of the intestinal microbiota of hundreds of healthy individuals, but also that of patients suffering from various pathologies (inflammatory bowel diseases, diabetes, obesity, liver pathologies...) demonstrated the importance of a symbiosis between the microbiota and its host. Dysbiosis of this ecosystem was associated with several diseases, and this allowed identifying bacterial species signatures of the patient's condition. It should be emphasized, however, that the contribution of this "dysbiotic" microbiota to the disease remains to be elucidated. Though, microbiota transplantation from human patients to germ-free animals established the importance of the gut microbiota to the disease. In order to decipher the mechanisms by which our commensal bacteria interact with human cells, an innovative functional metagenomic approach has been implemented allowing to identify bacterial genes and molecules / metabolites involved in this cross talk. The cutting-edge characterization of our other genome, our metagenome, remains a crucial step in the full understanding of the human body.
Research interests Hervé Blottière's main research interests are to understand the cross-talk between gut microbiota and the intestinal mucosa (epithelial and immune cells) and to look for molecular signals from the microbiota implicated in this cross-talk. His goals are to provide a better understanding of the physiology of the digestive tract and to allow strategies to prevent gut pathologies (inflammation, overweight, cancer).
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