Identification of a novel signaling network in Porphyromonas gingivalis

描述（申请人提供）：细菌细胞间的通讯是控制其行为、调节其致病性和提高其生存能力所必需的。细菌的合作特性是通过信号分子来完成的。最容易理解的细菌信号分子是细胞密度相关的（群体感应）自诱导剂。牙龈假单胞菌是一种革兰氏阴性厌氧菌，与成人牙周炎密切相关。牙龈卟啉卟啉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控。我们最近的研究表明，在较高的细胞密度下，fimA、hag和hmu基因的表达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，这表明luxS /AI-2系统不负责群体感应调节fimA基因的表达。基于这些观察结果，我们假设牙龈卟啉卟啉毒力基因的表达受到一种新的非ai -2自诱导剂的调控。为了验证假设，我们将首先确定负责群体感应调节fimA基因表达的群体感应信号。我们还将利用DNA微阵列分析研究牙龈假单胞菌群体感应信号调控基因。本应用程序中提出的研究结果应该为高度成功的周围病原体的进化提供新的见解，并揭示在细菌细胞-细胞通信过程中一些意想不到的机制。

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.