Determining the mechanism and impact of streptococcal RaS-RiPPs on the human oral microbiome

确定链球菌 RaS-RiPP 对人类口腔微生物组的作用机制和影响

• 批准号: 10560013
• 负责人: Britta Rued
• 金额: $ 11.17万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10560013
• 关键词: Achievement; Address; Adverse effects; Affect; Architecture; Award; Bacteria; Behavior; Biological; Biotinylation; Cells; Chemical Structure; Chicago; Co-Immunoprecipitations; Collaborations; Communities; Complex; Data; Dental caries; Disease; Environment; Epithelial Cells; Equilibrium; Faculty; Family; Foundations; Genetic Screening; Genetic Transcription; Goals; Growth; Health; Home; Human; Illinois; Immunobiology; In Vitro; Infective endocarditis; Institution; Investigation; Knowledge; Laboratory Research; Luciferases; Metagenomics; Methods; Microbe; Mutagenesis; Operon; Oral; Oral health; Organism; Peptide Biosynthesis; Peptides; Phase; Positioning Attribute; Process; Production; Productivity; Proteins; Proteomics; Quantitative Reverse Transcriptase PCR; Reporter; Research; Research Personnel; Ribosomes; S-Adenosylhomocysteine; S-Adenosylmethionine; Secure; Streptococcus; Streptococcus ferus; Streptococcus mitis; Streptococcus mutans; Streptococcus oralis; System; Training; Universities; Virus; Western Blotting; Work; career; comparative; dysbiosis; experimental study; member; metatranscriptomics; microbiome; microorganism; novel; opportunistic pathogen; oral cavity epithelium; oral commensal; oral microbial community; oral microbiome; oral pathogen; oral streptococci; peptide chemical synthesis; programs; quorum sensing; response; transcriptome sequencing; transcriptomics

PROJECT SUMMARY The human oral microbiome is home to a unique group of bacteria with the ability to affect the overall health of the human host: Streptococci spp. This group is involved in a wide range of diseases, from dental caries to infective endocarditis. They include important oral pathogens such as the cariogenic Streptococcus mutans and commensal organisms such as Streptococcus mitis. These important oral members produce a large array of radical-S-adenosylmethionine ribosomally synthesized and post-translationally modified peptides (RaS-RiPPs). The newly identified compounds include a wealth of chemical structures and have been found to inhibit the growth of other oral Streptococci, as well as modulate the behavior of producer organisms themselves. The initial goal of this proposal is to elucidate the mechanism of action of the RaS-RiPP tryglysin from S. mutans, and to examine its impact on the functional oral microbiome. Upon defining tryglysin’s mechanism of action on oral Streptococci and the oral microbiome, this study will be expanded to examine the biological significance of other RaS-RiPPs produced by Streptococci: streptosactin, suisactin, rotapeptides, and NxxC family peptides. While the chemical structure and synthesis of these peptides has been defined, the biological significance of these identified RaS-RiPPs is unexplored. Given the important status of Streptococci spp. to the health of the human oral microbiota, this represents a major gap in knowledge about a class of peptides with huge potential impacts on overall oral health. This proposal aims to create a research platform for studying RaS-RiPPs from oral Streptococci, defining their function, and examining shifts in the functional oral microbiome in response to their production. Executing this research program at the University of Illinois at Chicago (UIC) will allow for the establishment of the candidate as an independent researcher and provide avenues for the achievement of the candidate’s career goals: establishing a productive and first-rate research laboratory and securing a tenured faculty position at a major research institution.

项目摘要 人口腔微生物组是一组独特的细菌的家园，能够影响整体 人类宿主的健康：链球菌属。该小组参与了各种疾病，从牙科中 进行感染性心内膜炎。它们包括重要的口腔病原体，例如致癌链球菌 诱变和共生生物，例如链球菌。这些重要的口腔成员会产生 大阵列自由基 - 甲基甲硫代氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基二氨酸的合成和翻译后修饰的肽 （Ras-ripps）。新确定的化合物包括大量的化学结构，并被发现 抑制其他口服链球菌的生长，并调节生产者生物的行为 自己。该提案的最初目标是阐明Ras-Ripp Tryglysin的作用机理 来自S. mutans，并检查其对功能性口服微生物组的影响。定义Tryglysin的 对口服链球菌和口服微生物组的作用机制，将扩展该研究以检查 链球菌产生的其他RAS乳的生物学意义：链霉素，舒张肽，旋转肽， 和NXXC家庭胡椒粉。尽管已经定义了这些辣椒的化学结构和合成，但 这些发现的Ras-ripps的生物学意义是出乎意料的。鉴于链球菌的重要状态 spp。对于人类口服微生物群的健康，这代表了有关一类的知识的主要差距 对整体口腔健康产生巨大影响的肽。该建议旨在建立一个研究平台 用于研究口服链球菌的Ras-ripps，定义其功能，并检查功能的变化 口服微生物组响应其生产。在伊利诺伊大学执行此研究计划 芝加哥（UIC）将允许将候选人建立为独立研究人员，并提供 实现候选人职业目标的途径：建立一项富有成效的一流研究 实验室并确保在一家主要研究机构中担任终身教师职位。