Identification of a novel signaling network in Porphyromonas gingivalis

描述(申请人提供)：细菌细胞间的通讯对于控制它们的行为、调节它们的致病性和提高它们的生存能力是必要的。细菌的协作特征是通过信号分子完成的。最被理解的细菌信号分子是与细胞密度相关的(群体感应)自动诱导剂。牙龈假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。目前已鉴定出几个牙龈假单胞菌毒力基因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都受到调控。此外，在LuxS突变体中，这些基因的表达水平不受影响，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，我们假设牙龈假单胞菌中毒力基因的表达受一种新型的非AI-2自动诱导剂的调节。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控的群体感应信号。我们还将利用DNA微阵列技术对牙龈假单胞菌群体感应信号调控基因进行研究。本申请中提出的研究结果应该为高度成功的周围病原菌的进化提供新的见解，并阐明一些在细菌细胞-细胞通讯过程中发挥作用的意想不到的机制。 公共卫生相关性：牙龈假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。这项建议的目的是鉴定和研究一个群体感应分子，该分子负责诱导几个毒力基因的差异表达。这项工作的发现将为设计干预牙龈假单胞菌生物膜的启动和形成的药物提供新的机会。

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.