setCDQR regulon of the integrating and conjugative elements of the SXT/R391 family: a genetic and molecular study / Étude génétique et moléculaire du régulon setCDR des ICE SXT/R391

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Integrating conjugative elements (ICEs) are mobile gene clusters that are exchanged between bacteria during a direct cell-to-cell contact. ICEs allow microorganisms to exchange genes conferring an advantage in specific environments such as resistance to antibiotics and enhanced virulence. A family of ICE originally identified in Vibrio cholerae, the causative agent of the diarrheal disease cholera, is rapidly spreading among environmental and clinical strains of diverse human and animal pathogens dwelling in aquatic environments. As a consequence, this family of ICEs contributes to the rapid spread of multi-resistance to antibiotics within populations of pathogenic microorganisms worldwide. While the environmental stimuli that trigger the exchange of ICEs between bacteria are well known, the molecular mechanisms of this activation are not well understood. The goal of this research project is to investigate and understand in detail the cascade of events initiated by the stimulus (DNA-damaging agents such as UV light and some antibiotics) that leads to the exchange of ICEs between donor and recipient cells. We will study regulator proteins (activators and repressors) encoded by the ICEs that control the expression of ICE-borne genes involved in the formation of the mating bridge that connect the donor and recipient cell to allow ICE transfer. Furthermore, recent evidence indicate that some of these activators stimulate the expression of genes of the host bacterium together with ICE-borne genes. We will investigate the scale of this phenomenon in order to assess the impact of the acquisition of an ICE by a bacterial cell on the expression of its own genes and its virulence. This research project is part of a larger program aimed at understanding better the molecular aspects of the mechanisms of gene exchange between microorganisms, as well as the role of gene exchange on bacterial genome evolution and on the population dynamics of pathogens in aquatic environments.