权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Deciphering the Role of Rgg in the Pneumococcal Signaling, Colonization and Virulence Portfolio

解读 Rgg 在肺炎球菌信号传导、定植和毒力组合中的作用

基本信息

批准号：
10615705
负责人：
Natalia Luisa Hiller
金额：
$ 32.72万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-23 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10615705
关键词：
Adhesions Agonist Binding Binding Sites Biological Assay Cell physiology Cells Chronic Competence Complex Contracts DNA DNA-Protein Interaction Development Disease Disease model EMSA Enterococcus Family Future Galactose Genetic Genetic Transcription Glycoproteins Goals Growth Immune Evasion In Vitro Infection Knowledge Link Luciferases Mannose Maps Mediating Microbial Biofilms Molecular Molecular Probes Morbidity - disease rate Mucous Membrane Nasopharynx Nutrient Order Coleoptera Peptide Signal Sequences Peptides Phenotype Play Pneumococcal Colonization Pneumococcal Infections Pneumonia Post-Transcriptional Regulation Process Promoter Regions Proteins Public Health Regulation Reporter Role Series Signal Transduction Streptococcus Streptococcus pneumoniae Synthetic Peptide Libraries System Testing Tissues Transcriptional Regulation United States Virulence Work antagonist antimicrobial capsule design drug development improved in vivo innovation insight mortality mouse model promoter receptor spatiotemporal therapeutic development time use tool

项目摘要

Project Summary The overall goal of this project is to advance our understanding of pneumococcal colonization. Pneumococcal diseases are major causes of morbidity and mortality in the United States and worldwide, and colonization of the nasopharynx is the first step for pneumococcal infections. While much is known about phenotypes and cellular processes associated with pneumococcal colonization, the molecules coordinating these processes are not well understood. Our preliminary work characterizing the Rgg144- Shp144 regulator-peptide signal transduction system has lead us to hypothesize that this system plays a pivotal role in orchestrating pneumococcal colonization. At a broad level, our work will provide insight into pneumococcal colonization and the Rgg family of signal transduction systems, widely distributed in streptococci and enterococci. At a specific level, we will determine which colonization-associated phenotypes are regulated by Rgg144 and establish whether Rgg144 mediates these phenotypes via regulation of the capsule (Aim 1). We will to identify specific residues associated with peptide-regulator interactions and with regulator-DNA interactions (Aim 2). We will reveal SHP144-derived peptides that act as agonists and antagonists in vitro and in vivo, for use in manipulating the system in basic functional studies as well as future drug development efforts (Aim 2 and 3). We will provide an in vivo characterization of Rgg144 expression and activity in multiple tissues over time using two different murine models of pneumococcal infection (Aim 3). Together, our findings will uncover the contribution of Rgg144 to transcriptional regulation of the capsule, advance our understanding of pneumococcal colonization, and shed light on the development of anti-pneumococcal therapies. The work is innovative in that it approaches the study of Rggs by generating a spatio-temporal map of Rgg144 expression and activity during infection.

项目总结