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 人类口腔微生物组是一组独特的细菌的家园，这些细菌能够影响整个口腔的微生物。 人类宿主的健康：链球菌属这个群体涉及广泛的疾病，从牙科 龋齿到感染性心内膜炎它们包括重要的口腔病原体，如致龋链球菌 变形菌和微生物如缓症链球菌。这些重要的口腔成员产生了 大量的自由基-S-腺苷甲硫氨酸核糖体合成和后修饰肽 （RaS-RiPP）。新发现的化合物包括丰富的化学结构，并且已被发现 抑制其他口腔链球菌的生长，以及调节生产生物体的行为 自己该提案的最初目标是阐明RaS-RiPP胰蛋白酶的作用机制 来自酿脓链球菌变异，并检查其对功能性口腔微生物组的影响。在定义tryglysin的 对口腔链球菌和口腔微生物组的作用机制，这项研究将扩大到检查 由链球菌产生的其它RaS-RiPP的生物学意义：链菌素，suisactin，rotapeptides， 和NxxC家族肽。虽然已经定义了这些肽的化学结构和合成， 这些鉴定的RaS-RIPP的生物学意义尚未探索。鉴于链球菌的重要地位 spp.对人类口腔微生物群的健康，这代表了对一类 肽对整体口腔健康具有巨大的潜在影响。该项目旨在建立一个研究平台。 用于研究口腔链球菌中的RaS-RiPP，定义其功能，并检查功能性 口腔微生物组响应其生产。在伊利诺伊大学执行这项研究计划， 芝加哥大学（UIC）将允许候选人作为独立研究员，并提供 实现候选人职业目标的途径：建立一个富有成效的和一流的研究 实验室和确保终身教职的一个主要研究机构。