Identification of a novel signaling network in Porphyromonas gingivalis

点击翻译按钮获取中文摘要

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.