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

整合共轭元件（ICEs）是一种可移动的基因簇，在细菌之间的直接细胞与细胞接触中交换。ice允许微生物交换基因，从而在特定环境中获得优势，例如对抗生素的耐药性和增强的毒力。一个ICE家族最初在霍乱弧菌（腹泻病霍乱的病原体）中发现，正在水生环境中生活的各种人类和动物病原体的环境和临床菌株中迅速传播。因此，这一ice家族促进了全球病原微生物种群中抗生素多重耐药的迅速传播。虽然引发细菌间ICEs交换的环境刺激是众所周知的，但这种激活的分子机制尚不清楚。本研究项目的目标是详细调查和了解刺激（dna损伤剂，如紫外线和一些抗生素）引发的一系列事件，这些事件导致供体和受体细胞之间交换ICEs。我们将研究由ICE编码的调节蛋白（激活因子和抑制因子），这些蛋白控制ICE携带的基因的表达，这些基因参与形成连接供体和受体细胞的交配桥，以允许ICE转移。此外，最近的证据表明，这些激活剂中的一些可以刺激宿主细菌基因的表达以及ice携带的基因。我们将研究这种现象的规模，以评估细菌细胞获得ICE对其自身基因表达和毒性的影响。该研究项目是一个更大项目的一部分，旨在更好地了解微生物之间基因交换机制的分子方面，以及基因交换在细菌基因组进化和水生环境中病原体种群动态中的作用。

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.