Purine catabolites as inducers of bacterial gene expression

这个项目的总体目标是了解细菌病原体适应植物寄主环境的机制，这种适应对细菌的生存和毒力至关重要。了解这些机制是努力控制疾病进展所必需的。当细菌植物病原体感染宿主时，随后会发生一场拉锯战，在这场拉锯战中，植物宿主旨在保护自己免受病原体的攻击；细菌反过来做出反应，通常通过利用宿主衍生的信号来触发促进生存和毒力的特征的表达，从而颠覆宿主的防御。这个项目的重点是细菌检测和响应这种宿主信号的机制。此外，该项目通过为研究生和本科生提供获得研究经验和熟练掌握现代分子生物学技术的机会，将研究和教学结合在一起。研究生将在开发这些研究项目和传播成果方面发挥不可或缺的作用。对于本科生来说，他们中的许多人将从促进包容性和多样性的项目中招募，独立研究的机会将补充他们的常规课程，为他们的深造做好准备，并为发展一支有竞争力的STEM劳动力做出贡献。宿主产生活性氧，作为对细菌感染的防御。导致这种氧化爆发的酶之一是黄嘌呤脱氢酶，它将次黄嘌呤转化为黄嘌呤，并将黄嘌呤转化为尿酸盐。这个项目的第一个目标是解决这样的假设，即寄主植物在细菌感染期间产生的黄嘌呤和尿酸盐作为扩散信号在细菌中诱导差异基因表达。第二个目标是研究转录因子PECS在感知黄嘌呤和尿酸以及控制基因表达方面的作用。将实施RNA-SEQ和CHIP-SEQ相结合的方法来识别PECS调节子，并将确定从RNA-SEQ数据预测的PECS突变株的表型。以植物病原菌蚕豆根癌农杆菌为研究对象，比较野生型和PcS缺失突变株的毒力。明确寄主来源的信号和这些可扩散的信使在植物病原菌中触发毒力相关基因表达的机制将最终促进抗菌剂的开发。

The overall goal of this project is to understand mechanisms by which bacterial pathogens adapt to a plant host environment, an adaptation that is essential for bacterial survival and virulence. Knowing such mechanisms is required for efforts to control disease progression. When a bacterial plant pathogen infects a host, a tug-of-war ensues in which the plant host aims to defend itself against the pathogen; the bacterium in turn responds, often subverting host defenses by utilizing host-derived signals to trigger expression of traits that promote survival and virulence. This project focuses on mechanisms by which bacteria detect and respond to such host-derived signals. In addition, the program integrates research and teaching by offering the opportunity for both graduate and undergraduate students to acquire research experience and proficiency in modern molecular biology techniques. Graduate students will be integral to developing these research projects and in disseminating results. For undergraduate students, many of whom will be recruited from programs that promote inclusion and diversity, the opportunities for independent research will complement their regular course curriculum, prepare them for advanced studies, and contribute to the development of a competitive STEM workforce.Hosts produce reactive oxygen species as a defense against a bacterial infection. One of the enzymes responsible for this oxidative burst is xanthine dehydrogenase, which converts hypoxanthine to xanthine and xanthine to urate. The first objective of this project is to address the hypothesis that the xanthine and urate that are produced by host plants during a bacterial infection function as diffusible signals to induce differential gene expression in the bacterium. The second goal is to investigate the role of the transcription factor PecS in sensing xanthine and urate and controlling gene expression. A combination of RNA-seq and ChIP-seq will be implemented to identify the PecS regulon, and phenotypes of pecS mutant strains predicted from RNA-seq data will be determined. Focusing on the plant pathogen Agrobacterium fabrum, the virulence of wild-type and pecS deletion mutant strains will be compared. Defining host-derived signals and the mechanisms by which these diffusible messengers trigger expression of virulence-associated genes in plant pathogens will ultimately facilitate development of antibacterial agents.