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Pathway for functional characterization of hypothetical genes and non-coding RNAs of Enterococcus faecalis

粪肠球菌假设基因和非编码 RNA 功能表征途径

基本信息

批准号：
8986937
负责人：
GARY M DUNNY
金额：
$ 22.8万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8986937
关键词：
Antibiotic Resistance Antibiotic Therapy Biochemical Biological Assay Biology Centers for Disease Control and Prevention (U.S.)Chemicals Code Computing Methodologies Data Databases Disease Endocarditis Enterococcus faecalis Environment Experimental Models Future Genes Genetic Genetic Determinism Genetic Screening Genome Growth Hospitals In Vitro Infection Intercistronic Region Laboratories Lead Length Life Style Microarray Analysis Microbial Biofilms Modeling Molecular Molecular Mechanisms of Action Mutation Nosocomial Infections Opportunistic Infections Organism Oryctolagus cuniculus PAWR protein Pathogenicity Pathway interactions Peptides Pharmaceutical Preparations Physiological Physiology Positioning Attribute Production Proteins RNA Regulation Research Resources Role Structure Study models System Technology Tertiary Protein Structure Time Untranslated RNA Vaccines antimicrobial drug base fitness follow-up genome sequencing genome-wide genome-wide analysis in vivo interest mutant novel pathogen polypeptide protein function public health relevance recombinase research study transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): This project will examine the role of non-coding regulatory RNAs (ncRNAs) and hypothetical proteins of Enterococcus faecalis in adaptation to growth conditions relevant to opportunistic infections. E. faecalis is a leading cause of hospital-acquired infections whose treatment is impeded by the inherent and acquired antibiotic resistance of the organism, and by its propensity to adapt to growth and survival in hostile conditions, and by its ability to transition between commensal and pathogenic lifestyles. We will study the model laboratory strain OG1RF in both an in-vitro biofilm system (CDC biofilm reactor) and in an experimental endocarditis model. We will use a combination of computational searches, and a powerful new genetic screen we have termed "Smart TnSeq" to identify hypothetical proteins ncRNAs contributing to competitive fitness in these environments, and begin to study their targets and mechanisms of action. The results of this research will include the following: 1) A more comprehensive picture of the role of ncRNA regulation and hypothetical protein function in this organism under growth conditions relevant to its role in hospital infectios will emerge. 2) A workflow for genome-wide functional and mechanistic studies of regulation by E. faecalis ncRNAs and hypothetical proteins will be validated. 3) In the longer term, new drug and vaccine targets may be identified.