Identification of a novel signaling network in Porphyromonas gingivalis

描述（申请人提供）：细菌细胞间通讯是控制其行为、调节其致病性、增强其生存能力所必需的。细菌的合作特征是通过信号分子实现的。最好理解的细菌信号分子是细胞密度相关（群体感应）自诱导物。牙龈卟啉单胞菌是一种与成人牙周炎密切相关的厌氧革兰氏阴性细菌。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，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，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，我们假设牙龈卟啉单胞菌中毒力基因的表达受一种新型非AI-2自身诱导物的调控。为了验证假设，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。我们还将利用DNA微阵列技术研究牙龈卟啉单胞菌群体感应信号调控基因。本申请中提出的研究结果应该为非常成功的病原体的进化提供新的见解，并阐明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与成人牙周炎密切相关的厌氧革兰氏阴性细菌。本研究的目的是鉴定和研究一种能诱导多种毒力基因差异表达的群体感应分子。这项工作的发现应该提供新的机会，设计药物干扰牙龈卟啉单胞菌生物膜的启动和形成。

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.