牙龈卟啉单胞菌能量代谢基因群对其致病力影响的研究

Porphyromonas gingivalis, a key etiologic agent of chronic periodontitis, could invade into the host cells, avoid destruction by host defenses, and disturb cell's physiological functions. Recent results showed that the regulated genes of energetic metabolism are closely related to the virulence of the pathogen. These genes are very important for bacteria to react upon the changing circumstance and nutrition. Meanwhile, they could adjust the expression of other virulent factors of bacteria. The classification based on the fimA genotype of Pg is a useful method to scan the disease-related strain and identify the specific virulence of Pg. Our previous studies found that Pg-Ⅱ is closely correlated with chronic periodontitis in Chinese adult. After invading the gingival epithelial cells, Pg-Ⅱ specifically increased the expression of regulated genes of carbon and iron metabolism, which were designated as PG1676 and PG1858, suggesting the possible links between the regulated genes of energetic metabolism and the virulence of Pg-Ⅱ. In the present research, we planed to create the Pg PG1676/PG1858 mutant firstly. Then the differences between the Pg and mutants will be compared on the aspects of ⅰ) the morphology of bacteria; ⅱ) the biological characters of bacteria; ⅲ) the various aspects of bacteria's pathogenicity. The proteomic technologies will be adopted to scan and identify the key virulent proteins of Pg-Ⅱ correlated with the regulated genes of energetic metabolism, and the cluster analysis will be used to analyze the potential functions of these proteins. The aim of this research is to deeply clarify the specific pathogenicity of Pg-Ⅱby means of the functional proteomic analysis.

牙龈卟啉单胞菌（Pg）是牙周病重要致病菌，可迅速侵入细胞内逃避宿主免疫防御系统，并干扰细胞生理功能。最新研究显示：能量代谢基因群对胞内致病菌的毒力调控至关重要，是细菌应答环境营养压力、调节其它致病基因的重要调控元件。菌毛fimA基因分型是筛选牙周病相关性Pg高毒力菌株，鉴定Pg特异性致病力的有效途径。我们前期研究发现：ⅡfimA型Pg与中国成人慢性牙周炎密切相关，具有高致病性；侵入上皮细胞的Ⅱ型Pg特异性上调碳源及铁代谢相关基因PG1676和PG1858的表达。提示：能量代谢基因群与Ⅱ型Pg高毒力存在明显关联。本研究拟体外构建PG1676和PG1858基因缺陷株，比较Pg野生株与缺陷株的细菌表型、生物学特性及各项致病力差异；通过蛋白组学技术鉴定能量代谢基因群调控的Ⅱ型Pg关键致病蛋白，生物信息学聚类分析其功能，最终从功能蛋白组角度阐明Ⅱ型Pg高致病性的分子机制，为牙周病生态防治提供新思路。

牙龈卟啉单胞菌（Pg）是牙周疾病的重要致病菌，可迅速侵入细胞内逃避宿主免疫防御系统。最新研究显示能量代谢基因群对胞内致病菌的毒力调控至关重要。我们前期研究发现ⅡfimA型Pg与中国成人慢性牙周炎密切相关，具有高致病性；侵入上皮细胞的Ⅱ型Pg特异性上调碳源及铁代谢相关基因PG1676和PG1858的表达。提示：能量代谢基因群与Ⅱ型Pg高毒力存在明显关联。本研究通过体外构建PG1676和PG1858基因缺陷株，比较Pg野生株与缺陷株的细菌表型、生物学特性及各项致病力差异，明确了 PG1676 参与PgW83重要毒力因子凝集素及牙龈素的调控，在一定程度上揭示了Pg高致病性的分子机制，为牙周病生态防治提供了新的实验依据和理论基础，具有一定的指导意义。