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The irvA-dependent pathway: a link between stress adaptation and virulence

irvA 依赖性途径：应激适应与毒力之间的联系

基本信息

批准号：
8403390
负责人：
Justin Merritt
金额：
$ 28.47万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-12 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8403390
关键词：
Acids Address Affect Bacterial Infections Bacteriophage lambda Binding Binding Sites Biochemical Biological Assay ChIP-on-chip Characteristics Chloramphenicol Chloramphenicol Resistance Competence DNA Binding Data Dental Plaque Dental caries Disease Engineering Escherichia coli Exhibits Felis catus Future Gene Chips Gene Expression Gene Expression Regulation Gene Mutation Gene Targeting Genes Genetic Genetic Programming Genetic Transcription Genome Genomics Goals Human In Vitro Induced Mutation Intercistronic Region Libraries Link Maps Mediating Mediator of activation protein Microbial Biofilms Modeling Mutation Mutation Analysis Organism Pathogenesis Pathogenicity Pathway interactions Peptide Hydrolases Phenotype Post-Translational Regulation Production Proteins Regulation Regulator Genes Regulatory Pathway Regulon Reporter Repression Research Role Sampling Sensory Signal Transduction Site Slide Streptococcus mutans Stress System Technology Testing Transducers Translating Virulence Virulence Factors Western Blotting Work bacteriocin base biological adaptation to stress chromatin immunoprecipitation design genetic analysis genetic regulatory protein in vivo insight member mutant novel oral biofilm paralogous gene public health relevance response stress tolerance transcription factor treatment strategy

项目摘要

DESCRIPTION (provided by applicant): The proposed research aims to investigate the genetic and biochemical mechanisms of gene regulation in Streptococcus mutans through the irvA-dependent pathway. The goals of this project will be achieved in three aims by: 1) Analyzing the mechanism of irvA induction 2) Identifying the IrvA regulon 3) Characterizing the genetic regulators that comprise the irvA-dependent pathway. 1) To analyze the mechanism of irvA induction, we will perform detailed biochemical studies of key residues of SMu1275 to determine how its endogenous autocleavage capacity can modulate its ability to control irvA expression. 2) To identify the IrvA regulon, we will employ chromatin immunoprecipitation and microarray (ChIP-chip). Using specially designed Affymetrix Genechips(R), we will be able to detect most or all of the IrvA binding sites in vivo. Transcription analysis of these genes will determine the role of IrvA as a transcription regulator of genes associated with stress and virulence related phenotypes. 3) To characterize the genetic regulators of the irvA-dependent pathway, we will first identify the genes that are capable of inducing irvA. Genetic analyses will then examine the role of irvA as a mediator of stress and virulence related phenotypes in these strains. Finally, genes coregulated with the irvA-dependent pathway will be identified. The goal of this project is to use the irvA-dependent pathway as a model to examine the connection between stress adaptation and the regulation of important virulence factors of Streptococcus mutans. Since the long-term persistence of S. mutans requires the coordination of stress response mechanisms and virulence factor gene expression, these data may yield new insights into S. mutans cariogenicity.

描述（由申请人提供）：拟议的研究旨在研究变形链球菌通过irvA依赖性途径进行基因调控的遗传和生化机制。本项目的目标将通过以下三个方面实现：1）分析irvA诱导的机制2）鉴定IrvA调节子3）表征组成irvA依赖性途径的遗传调节因子。1)为了分析irvA诱导的机制，我们将对SMu 1275的关键残基进行详细的生化研究，以确定其内源性自切割能力如何调节其控制irvA表达的能力。2)为了鉴定IrvA调节子，我们将采用染色质免疫沉淀和微阵列（ChIP芯片）。使用专门设计的Affyssin Genechips（R），我们将能够在体内检测大部分或所有的IrvA结合位点。这些基因的转录分析将确定IrvA作为与胁迫和毒力相关表型相关的基因的转录调节因子的作用。3)为了表征irvA依赖性途径的遗传调节因子，我们将首先鉴定能够诱导irvA的基因。遗传分析将检查irvA作为这些菌株中压力和毒力相关表型的介体的作用。最后，将确定与irvA依赖性途径共调节的基因。本项目的目标是使用irvA依赖性途径作为模型来检查变形链球菌的应激适应和重要毒力因子的调节之间的联系。由于S.变形链球菌需要胁迫应答机制和毒力因子基因表达的协调，这些数据可能会产生新的见解S。致龋性变形杆菌。