Purine catabolites as inducers of bacterial gene expression

嘌呤分解代谢物作为细菌基因表达的诱导剂

• 批准号: 1714219
• 负责人: Anne Grove
• 金额: $ 69.06万
• 依托单位: Louisiana State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1714219&HistoricalAwards=false
• 关键词: Purine; catabolites; inducers; bacterial; gene

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.

该项目的总体目标是了解细菌病原体适应植物宿主环境的机制，这种适应对于细菌的生存和毒力至关重要。了解这些机制是控制疾病进展的必要条件。当细菌性植物病原体感染宿主时，就会发生一场拉锯战，植物宿主的目的是保护自己免受病原体的侵害。细菌反过来做出反应，通常利用宿主来源的信号触发促进生存和毒力的特征表达，从而破坏宿主的防御。该项目重点研究细菌检测和响应此类宿主信号的机制。此外，该项目将研究和教学融为一体，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。研究生将成为开发这些研究项目和传播成果的重要组成部分。对于本科生来说，其中许多人将从促进包容性和多样性的项目中招收，独立研究的机会将补充他们的常规课程，为他们的高级研究做好准备，并有助于培养有竞争力的 STEM 劳动力。宿主会产生活性氧来防御细菌感染。负责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。该项目的第一个目标是解决这样的假设：宿主植物在细菌感染期间产生的黄嘌呤和尿酸盐充当可扩散信号以诱导细菌中的差异基因表达。第二个目标是研究转录因子 PecS 在感知黄嘌呤和尿酸盐以及控制基因表达中的作用。将结合RNA-seq和ChIP-seq来鉴定PecS调节子，并确定从RNA-seq数据预测的pecS突变株的表型。将重点关注植物病原体农杆菌，比较野生型和 pecS 缺失突变株的毒力。定义宿主来源的信号以及这些可扩散信使触发植物病原体中毒力相关基因表达的机制将最终促进抗菌剂的开发。

项目成果

Transcription Factor PecS Mediates Agrobacterium fabrum Fitness and Survival

• DOI: 10.1128/jb.00478-22
• 发表时间: 2023-06-14
• 期刊: JOURNAL OF BACTERIOLOGY
• 影响因子: 3.2
• 作者: Nwokocha，George C.;Adhikari，Prava;Grove，Anne
• 通讯作者: Grove，Anne

The Link between Purine Metabolism and Production of Antibiotics in Streptomyces

• DOI: 10.3390/antibiotics8020076
• 发表时间: 2019-06
• 期刊: Antibiotics
• 作者: Smitha Sivapragasam;A. Grove

Do Global Regulators Hold the Key to Production of Bacterial Secondary Metabolites?

全球监管机构掌握细菌次生代谢产物生产的关键吗？

• DOI: 10.3390/antibiotics8040160
• 发表时间: 2019
• 期刊: Antibiotics
• 作者: Thapa, Sudarshan Singh;Grove, Anne
• 通讯作者: Grove, Anne

The Global Regulator MftR Controls Virulence and Siderophore Production in Burkholderia thailandensis

• DOI: 10.1128/jb.00237-22
• 发表时间: 2022-10
• 期刊: Journal of Bacteriology
• 影响因子: 3.2
• 作者: S. Thapa;A. Al-Tohamy;A. Grove

A role for Vibrio vulnificus PecS during hypoxia

• DOI: 10.1038/s41598-019-39095-4
• 发表时间: 2019-02-26
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Bhattacharyya, Nabanita;Lemon, Tiffany L.;Grove, Anne
• 通讯作者: Grove, Anne