Identification of a novel signaling network in Porphyromonas gingivalis

牙龈卟啉单胞菌中新型信号网络的鉴定

基本信息

批准号：
8047740
负责人：
HUA XIE
金额：
$ 23.61万
依托单位：
MEHARRY MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2013-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8047740
关键词：
Adult Affect Animals Bacteria Bacterial Infections Behavior Cell Communication Cell Density Cells Commit DNA Microarray Chip DNA Sequence Analysis Drug Design Evolution Family Future Gene Expression Gene Expression Regulation Genes Goals Gram-Negative Anaerobic Bacteria Gram-Negative Bacteria Gram-Positive Bacteria Hemagglutinin Human Laboratories Lead Light Microarray Analysis Microbial Biofilms Oligopeptides Organism Pathogenicity Periodontitis Population Density Porphyromonas gingivalis Protein Subunits Proteins Pseudomonas Regulation Regulon Reporting Signal Transduction Signaling Molecule Staging System Testing Transcription Coactivator VAI-2 Vibrio Vibrio fischeri Virulence Work base fimbria heme-binding protein homoserine lactone insight intercellular communication mutant novel novel therapeutic intervention periopathogen quorum sensing response

项目摘要

DESCRIPTION (provided by applicant): The bacterial cell-cell communications is necessary for controlling their behaviors, regulating their pathogenicities, and enhancing their survival abilities. Cooperative features of bacteria are accomplished through signaling molecules. The best understood bacterial signaling molecules are cell-density related (quorum sensing) autoinducers. P. gingivalis is an anaerobic gram- negative bacterium that is strongly associated with adult periodontitis. Several virulence genes of P. gingivalis have been identified as quorum sensing-related genes. It appears that AI-2 is involved in regulation of these gene expressions. Our recent studies demonstrated expression of fimA, hag, and hmu genes are modulated at the transcriptional and translational levels at a higher cell density. Moreover, expression levels of these genes are not affected in a luxS mutant, suggesting that LuxS/AI-2 system is not responsible for quorum sensing regulation of fimA gene expression. Based on these observations, we hypothesize that expression of virulence genes in P. gingivalis is regulated by a novel non-AI-2 autoinducer. To test hypothesis, we will first identify the quorum sensing signal responsible for quorum sensing regulation of fimA gene expression. We will also investigate the quorum sensing signal- regulated genes in P. gingivalis by using DNA microarray analysis. The results of the studies proposed in this application should provide new insights into the evolution of a highly successful periopathogen and shed light on some unexpected mechanisms that function during bacterial cell-cell communication. PUBLIC HEALTH RELEVANCE: P. gingivalis is an anaerobic gram-negative bacterium that is strongly associated with adult periodontitis. The goal of this proposal is to identify and study a quorum sensing molecule responsible for induction of differential expression of several virulence genes. Findings from this work should provide new opportunities to design drugs to interfere with initiation and formation of the P. gingivalis biofilms.

描述（由申请人提供）：细菌细胞间的通讯对于控制其行为、调节其致病性和增强其生存能力是必要的。细菌的合作特征是通过信号分子实现的。最了解的细菌信号分子是细胞密度相关（群体感应）自诱导剂。牙龈卟啉单胞菌是一种厌氧革兰氏阴性细菌，与成人牙周炎密切相关。牙龈卟啉单胞菌的几个毒力基因已被鉴定为群体感应相关基因。 AI-2 似乎参与了这些基因表达的调节。我们最近的研究表明 fimA、hag 和 hmu 基因的表达在较高的细胞密度下在转录和翻译水平上受到调节。此外，这些基因的表达水平在luxS突变体中不受影响，表明LuxS/AI-2系统不负责fimA基因表达的群体感应调节。基于这些观察结果，我们假设牙龈卟啉单胞菌毒力基因的表达受到一种新型非 AI-2 自诱导剂的调节。为了检验假设，我们将首先确定负责 fimA 基因表达的群体感应调节的群体感应信号。我们还将通过 DNA 微阵列分析研究牙龈卟啉单胞菌中的群体感应信号调节基因。本申请中提出的研究结果应该为高度成功的周病原体的进化提供新的见解，并揭示细菌细胞间通讯过程中发挥作用的一些意想不到的机制。公共卫生相关性：牙龈卟啉单胞菌是一种厌氧革兰氏阴性细菌，与成人牙周炎密切相关。该提案的目标是识别和研究负责诱导几种毒力基因差异表达的群体感应分子。这项工作的结果应该为设计干扰牙龈卟啉单胞菌生物膜的启动和形成的药物提供新的机会。