Vibrio cholerae quorum sensing as an intestinal symbiosis factor in a model arthropod host

霍乱弧菌群体感应作为节肢动物模型宿主肠道共生因子

• 批准号: 10619004
• 负责人: PAULA I WATNICK
• 金额: $ 69.24万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10619004
• 关键词: Acetates; Arthropods; Bacteria; Cell Density; Central Nervous System; Chitinase; Cholera; Cholera Toxin; Communication; Complex; Data; Diarrhea; Dietary Supplementation; Digestion; Drosophila genus; Drosophila melanogaster; Enzymes; Epidemic; Epidemiology; Epithelial Cells; Epithelium; Extracellular Space; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Models; Genetic Transcription; Goals; Growth; Homeostasis; Human; Immune; Immune signaling; Infection; Innate Immune Response; Insecta; Intestines; Investigation; Kynurenine; Laboratories; Lipids; Longevity; Mammals; Measures; Mediating; Membrane; Metabolic; Metabolic Pathway; Metabolism; Microbe; Modeling; Mucous body substance; Natural Immunity; Nutrient; Organism; Outcome; Pathway interactions; Peptide Hydrolases; Peripheral; Pilum; Play; Regulation; Regulatory Pathway; Reporting; Repression; Role; Serotonin; Signal Pathway; Signal Transduction; Steroids; Symbiosis; TNF gene; Thinness; Toxin; Tryptophan; Tryptophan 5-monooxygenase; Tryptophan Metabolism Pathway; Vibrio cholerae; Virulence; Virulence Factors; Work; bacterial genetics; cell type; chromatin remodeling; enteric pathogen; epithelial repair; experimental study; genomic tools; gut microbiota; human pathogen; insulin signaling; intestinal epithelium; knock-down; membrane synthesis; metabolomics; microbial; pandemic disease; pathogen; programs; quorum sensing; response; symbiont; transcription factor; transcriptome sequencing

Abstract/Project Summary Vibrio cholerae is a human diarrheal pathogen and an environmental organism that persists in the arthropod intestine. Our preliminary results suggest that the V. cholerae high cell density quorum sensing regulator HapR orchestrates the metabolic transition of this microbe from intestinal pathogen to intestinal symbiont by extending host life span, activating host innate immunity and epithelial repair mechanisms, and promoting host metabolic homeostasis. Here we use the powerful genetics of the model arthropod Drosophila melanogaster to understand the lines of communication between host and pathogen that underlie this transition. We will identify bacterial metabolites that activate host innate immunity and trace the host pathways that are co-opted by the bacterium for this purpose. We will determine whether the arthropod intestinal mucus or peritrophic membrane supports growth of V. cholerae and whether digestion by HapR-activated degradative enzymes activates peritrophic membrane synthesis. Finally, we will explore the role of V. cholerae-derived tryptophan in promoting host metabolic homeostasis. These studies not only expand our appreciation of the role of V. cholerae HapR in the host-pathogen interaction but also provide a new paradigm of quorum sensing control of the host-microbe symbiosis.

摘要/项目摘要 Vibrio霍乱是一种人类腹泻病原体，是一种持续在节肢动物中的环境生物 肠。我们的初步结果表明V.霍乱高细胞密度群体传感调节剂 HAPR策划了该微生物从肠道病原体到肠道共生体的代谢过渡 延长宿主寿命，激活宿主先天免疫和上皮修复机制，并促进宿主 代谢稳态。在这里，我们使用模型Arthropod果蝇的强大遗传学 了解这一过渡的基础的宿主和病原体之间的交流线。 我们将确定激活宿主先天免疫力并追踪宿主途径的细菌代谢产物 为此目的由细菌选择。我们将确定节肢动物肠粘液还是 嗜营养膜支持V.霍乱的生长以及HAPR激活降解的消化是否存在 酶激活营养性膜合成。最后，我们将探索V.霍乱源的作用 色氨酸促进宿主代谢稳态。这些研究不仅扩大了我们对 V.霍乱HAPR在宿主 - 病原体相互作用中的作用，但也提供了新的Quorum Sensing范式 控制宿主微叶共生。

项目成果

Vibrio cholerae high cell density quorum sensing activates the host intestinal innate immune response.

• DOI: 10.1016/j.celrep.2022.111368
• 发表时间: 2022-09-20
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Jugder, Bat-Erdene;Batista, Juliana H.;Gibson, Jacob A.;Cunningham, Paul M.;Asara, John M.;Watnick, Paula I.
• 通讯作者: Watnick, Paula I.