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

SXT/R391 家族整合和共轭元件的 setCDQR 调节：遗传和分子研究 / âtude génétique et moléculaire du régulon setCDR des ICE SXT/R391

• 批准号: 326810-2011
• 负责人: Burrus, Vincent
• 金额: $ 4.08万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=526709
• 关键词: setCDQR; regulon; integrating; conjugative; elements

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.

整合接合元件（ICE）是在细胞与细胞直接接触期间在细菌之间交换的可移动基因簇。 ICE 允许微生物交换基因，从而在特定环境中具有优势，例如对抗生素的耐药性和增强的毒力。最初在霍乱弧菌（腹泻病霍乱的病原体）中发现的 ICE 家族，正在水生环境中的多种人类和动物病原体的环境和临床菌株中迅速传播。因此，该 ICE 家族导致了全球病原微生物群体中抗生素多重耐药性的快速传播。虽然引发细菌之间 ICE 交换的环境刺激众所周知，但这种激活的分子机制尚不清楚。该研究项目的目标是详细调查和了解由刺激（DNA 损伤剂，如紫外线和一些抗生素）引发的级联事件，这些事件导致供体和受体细胞之间的 ICE 交换。我们将研究 ICE 编码的调节蛋白（激活剂和阻遏蛋白），这些蛋白控制 ICE 携带的基因的表达，这些基因参与连接供体和受体细胞以允许 ICE 转移的交配桥的形成。此外，最近的证据表明，其中一些激活剂可以刺激宿主细菌的基因以及 ICE 携带的基因的表达。我们将调查这种现象的规模，以评估细菌细胞获得 ICE 对其自身基因表达及其毒力的影响。该研究项目是一个更大计划的一部分，旨在更好地了解微生物之间基因交换机制的分子方面，以及基因交换对细菌基因组进化和水生环境中病原体种群动态的作用。