The regulation of natural competence for DNA uptake and gene transfer in Salmonella and related bacteria

沙门氏菌及相关细菌 DNA 摄取和基因转移自然能力的调节

• 批准号: RGPIN-2019-07135
• 负责人: Cameron, Andrew
• 金额: $ 3.64万
• 依托单位: University of Regina
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=690180
• 关键词: regulation; natural; competence; DNA; uptake

OBJECTIVE: The proposed program will improve our understanding of how, when, and why many bacteria consume extracellular DNA using a process called “natural competence”. Although widespread, the contributions of natural competence to bacterial ecology and genome evolution remain poorly understood and poorly quantified. We seek to fill these large gaps in our understanding of DNA uptake, gene transfer, and DNA metabolism using well-studied species that have so far been overlooked in studies of natural competence.******BACKGROUND: Natural competence is a specialized and dedicated process involving active binding and translocation of DNA across the bacterial cell envelope. Once inside, DNA can recombine with the host genome, resulting in horizontal gene transfer through “natural transformation”. Horizontal gene transfer has broad and strong influences on genome evolution and niche expansion in bacteria. Escherichia coli, Salmonella, and their relatives are a group of adaptable bacteria that regularly transition between diverse environments. Members of this family evolve quickly through the acquisition of pathogenicity and antimicrobial resistance genes by horizontal gene transfer, but there is no knowledge of how often or when gene transfer through natural competence and transformation. DNA uptake provides valuable nutrients, and natural competence has been shown to support E. coli growth in nutrient limited environments, suggesting that competence has multiple ecological roles and consequences, from gene transfer to nutrient acquisition.******Our goal is to identify and characterize the molecular networks that link competence gene regulatory mechanisms to environmental and physiological signals in E. coli and Salmonella, and related bacteria. As we develop the abilities to naturally and artificially stimulate competence, we will quantify how DNA uptake contributes to gene transfer and nutrient acquisition in different bacterial environments. ******SCIENTIFIC APPROACH: This NSERC Discovery proposal addresses three integrated goals for studying Enterobacteriaceae. First, we will determine how natural competence is regulated in response to environmental and physiological signals. Second, we will quantify how natural competence contributes to horizontal gene transfer and genome evolution. And third, we will quantify how natural competence contributes to nutrient acquisition by bacteria in pure and mixed-species communities.******SIGNIFICANCE: Our Discovery program is poised to elucidate an ancient yet cryptic process in Salmonella, E. coli, and related bacteria. Natural competence is conserved over long evolutionary times and in diverse niches, indicating fundamental yet uncharacterized contributions to bacterial survival. The proposed Discovery program will build from our recent achievements to advance the study of natural competence and gene transfer.**

目的：提出的计划将提高我们对许多细菌如何，何时以及为什么使用称为“自然能力”的过程消耗细胞外DNA的理解。尽管广泛存在，但自然能力对细菌生态学和基因组进化的贡献仍然知之甚少，并且难以量化。我们试图填补这些巨大的空白，在我们的理解DNA摄取，基因转移，和DNA代谢使用充分研究的物种，迄今为止被忽视的研究自然能力。******背景：自然能力是一个专门的和专门的过程，涉及DNA在细菌细胞包膜上的主动结合和易位。一旦进入，DNA就可以与宿主基因组重组，通过“自然转化”进行水平基因转移。水平基因转移对细菌基因组进化和生态位扩展具有广泛而强烈的影响。大肠杆菌、沙门氏菌和它们的近亲是一群适应性强的细菌，它们经常在不同的环境中过渡。该家族的成员通过水平基因转移获得致病性和抗微生物药物耐药性基因而迅速进化，但不知道基因通过自然能力和转化转移的频率或时间。DNA摄取提供了有价值的营养，并且自然能力已被证明支持大肠杆菌在营养有限的环境中生长，这表明能力具有多种生态作用和后果，从基因转移到营养获取。******我们的目标是识别和表征大肠杆菌和沙门氏菌以及相关细菌中连接能力基因调控机制与环境和生理信号的分子网络。随着我们开发自然和人工刺激能力的能力，我们将量化DNA摄取如何在不同的细菌环境中促进基因转移和营养获取。******科学方法：这个NSERC发现提案解决了研究肠杆菌科的三个综合目标。首先，我们将确定自然能力是如何根据环境和生理信号进行调节的。其次，我们将量化自然能力如何促进水平基因转移和基因组进化。第三，我们将量化自然能力如何促进细菌在纯物种和混合物种群落中的营养获取。******意义：我们的发现计划准备阐明沙门氏菌，大肠杆菌和相关细菌的古老而神秘的过程。自然能力在漫长的进化时间和不同的生态位中是保守的，这表明了对细菌生存的基本但未被描述的贡献。提出的“发现”计划将以我们最近的成就为基础，推进自然能力和基因转移的研究