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Integrated transcriptomics and metabolomics approach to define pathogenicity of P.gingivalis

综合转录组学和代谢组学方法确定牙龈卟啉单胞菌的致病性

基本信息

批准号：
10458813
负责人：
Sasanka S Chukkapalli
金额：
$ 14.62万
依托单位：
TEXAS ENGINEERING EXPERIMENT STATION
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-30 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10458813
关键词：
Anaerobic Bacteria Animal Model Anti-Inflammatory Agents Atherosclerosis Bacterial Genes Biological Markers Cells Chronic Coronary artery Coupled Data Development Endothelial Cells Endothelium Environment Event Future Gene Expression Gene Expression Profile Genes Genetic Transcription Gingiva Goals High Pressure Liquid Chromatography Host Defense Human Immune response Impairment Infection Infection Control Inflammatory Invaded Lipoproteins Messenger RNA Metabolic Metabolic Pathway Molecular Nature Operon Organism Outcome Pathogenesis Pathogenicity Pattern Periodontal Diseases Periodontitis Porphyromonas gingivalis Protein-arginine deiminase Regulation Resolution Risk Role Signal Transduction System Systemic disease Technology Testing Tooth Loss Virulence Virulence Factors Work chronic infection design effective therapy endopeptidase Clp endothelial dysfunction gingipain innovation insight lipidome metabolome metabolomics microbial mutant next generation pathogen prevent protein-histidine kinase response specific biomarkers targeted treatment transcriptome sequencing transcriptomics treatment strategy

项目摘要

Project abstract Porphyromonas gingivalis (Pg), a gram-negative asaccharolytic anaerobe, is a major causative pathogen of chronic periodontitis. Pg not only causes tooth loss, but is also associated with increased risk for other systemic diseases such as atherosclerosis. Endothelial cells provide an interface for the systemic dissemination of Pg. Pg evades endothelial cell defenses and persist within endothelial cells, thereby allowing chronic infections like periodontal disease and systemic diseases to develop. Pg persistence can also leads to endothelial dysfunction resulting in impaired inflammatory signals and atherosclerosis. Hence, it is critical to understand the mechanisms of Pg infection of endothelial cells. Our central hypothesis is that Pg invades endothelial cells and evades host defenses by regulating its gene expression and metabolic requirements to survive within endothelial cells. To test this hypothesis, we propose to employ an innovative approach of integrating transcriptomics and metabolomics to better understand the pathogenic nature of Pg and its interaction with the endothelial cells. This comprehensive approach of combining dual RNA-seq and metabolomics data will identify significant gene- metabolite integrated networks that are unique to Pg infection of endothelial cells. Consequently, these studies will define those metabolic changes that occur during intracellular adaptation and survival of Pg and provide much needed fundamental insights into periodontal disease and systemic diseases associated with Pg. In order to achieve this goal, we propose the following specific aims. Aim 1: To determine and compare the RNA expression patterns of P. gingivalis (W83, W83Δ0717 & W83Δ0717::0717) and host cells (HMVEC and HCAEC) during the invasion and persistence states. Aim 2: To define the metabolomic changes that occur during the invasion and persistence states of P. gingivalis (W83, W83Δ0717 & W83Δ0717::0717) in HMVEC and HCAEC cells. These studies will be the first to characterize the mRNA and metabolite patterns of both Pg and host cells during pathogenesis. The expected outcome of this work is a comprehensive understanding of what molecular mechanism(s) specific to gene-metabolite networks Pg utilizes during invasion and persistence states. The successful completion of the proposed studies will lay the groundwork for developing effective treatment strategies to prevent PD and its associated systemic diseases.

项目摘要