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

目的：该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。虽然广泛存在，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，也很少量化。我们试图填补这些巨大的差距，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。背景技术背景：天然感受态是一个专门的和专用的过程，涉及DNA的主动结合和易位穿过细菌细胞包膜。一旦进入，DNA可以与宿主基因组重组，通过“自然转化”导致水平基因转移。基因水平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、沙门氏菌和它们的亲戚是一群适应性强的细菌，它们经常在不同的环境中转换。该家族的成员通过水平基因转移获得致病性和抗微生物抗性基因而迅速进化，但不知道通过天然感受态和转化进行基因转移的频率和时间。DNA的摄取提供了有价值的营养物质，而天然的感受态已被证明支持E。大肠杆菌生长在营养有限的环境中，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。我们的目标是确定和表征的分子网络连接的感受态基因调控机制，环境和生理信号在大肠杆菌。大肠杆菌和沙门氏菌以及相关细菌。 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：NSERC的发现提案提出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调节响应环境和生理信号。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有助于细菌在纯物种和混合物种群落中获得营养。意义：我们的探索计划准备阐明沙门氏菌，大肠杆菌中一个古老而神秘的过程。大肠杆菌和相关细菌。自然能力是保守的，在漫长的进化时间和不同的生态位，表明基本的，但未表征的贡献，细菌的生存。拟议的发现计划将建立在我们最近的成就，以推进自然能力和基因转移的研究。

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.**