Oral Pathogens: Polymicrobial Virulence Interactions

产品说明：人类主要的多种微生物感染在临床上表现为牙周病，其折磨50岁以下人口的近一半，并且与龈下沟定殖的微生物生物膜的发展有关。所提出的发病机制是多种多样的，大部分是由于复杂的微生物群落组成的许多细菌分类群，病毒和真菌。然而，这些龈下微生物聚生体中的某些始终与已经充分记录在临床环境中发生的sot和硬组织的进行性破坏相关（即，牙周炎）。各种体内和体外研究表明，选定的物种在龈下生态的优势，从微生物的协同和拮抗关系的结果。这些都与殖民地的可用表面，可用的营养物质和存在于社区内的生理“食物网”的性质有关。分子微生物学研究已经描述了近500种可以栖息在这个生态位的细菌，尽管在进行性组织破坏的部位已经描述了几种特定的微生物复合体。在大多数成人牙周炎患者中鉴定的主要聚生体由牙龈卟啉单胞菌、TannereIla althensis [Bacteroides althus]和齿垢密螺旋体组成。已提出该聚生体与疾病的相关性是由于组分物种之间的协同生理、宿主逃避和/或组织破坏能力。该R01申请的目的是测试这样的假设，即该多微生物聚生体包含协同增加组织破坏性宿主反应的"毒力网"，并且聚生体不太有效地改变宿主免疫反应。本研究拟通过动物模型系统来验证这一假说：（1）确定牙龈卟啉单胞菌、T.目的：（1）确定多微生物感染后获得性体液免疫应答的特征及其调节颅骨骨吸收的能力;（2）确定多微生物免疫后获得性体液免疫应答的特征及其调节骨吸收的能力。本研究的长期目标将是记录微生物相互作用、毒力协同作用、表征获得性和主动免疫应答，并将这些与组织破坏和骨吸收的改变相关。该应用的重要性在于，临床观察表明口腔微生物能够易位到循环中并全身表现为心内膜炎、脑/肾/肺和腹腔内感染，并导致糖尿病、冠状动脉疾病、骨质疏松症、肥胖症和早产的风险。因此，宿主对这些慢性感染的反应必须被视为对一般健康至关重要。

DESCRIPTION: The predominant polymicrobic infection of mankind is expressed clinically as periodontal disease, which afflicts nearly one-half of the population by 50 years of age, and is related to development of a microbial biofilm colonizing the subgingival sulcus. The suggested mechanisms of pathogenesis are varied, in most part due to the complex microbial community consisting of numerous bacterial taxa, viruses, and fungi. Nevertheless, certain of these subgingival microbial consortia are consistently correlated with a progressive destruction of sot_ and hard tissue that have been well documented to occur in clinical settings (i.e., periodontitis). Various in vivo and in vitro investigations have suggested that the dominance of selected species in the subgingival ecology results from both microbial synergistic and antagonistic relationships. These have been linked to the nature of available surfaces for colonization, available nutrients, and physiologic "food webs" that exists within the community. Molecular microbiologic studies have described nearly 500 species of bacteria that can inhabit this ecological niche, although several specific microbial complexes have been described at sites of progressing tissue destruction. A predominant consortia identified in a majority of adult periodontitis patients consists of Porphyromonas gingivalis, TannereIla forsythensis [Bacteroides forsythus], and Treponema denticola. The correlation of this consortium with disease has been proposed to result from synergistic physiological, host evasion, and/or tissue destructive capabilities among the component species. The objectives of this R01 application are to test a hypothesis that this polymicrobic consortium comprises a "virulence web" that synergistically increases tissue destructive host responses, and the consortia to be less effective modify that host immune responses. Three Specific Aims are proposed using an animal model system to test this hypothesis: (1) To determine molecular interbacterial synergistic virulence effects of P. gingivalis, T. forsythensis, and T denticola in an in vivo calvarial bone resorption model, (2) To determine the characteristics of acquired humoral immune responses to a polymicrobial infection and the ability of this response to modulate in vivo calvarial bone resorption, and (3) To determine the characteristics of active humoral immune responses to polymicrobial immunization and ability of this response to modulate bone resorption. The long-range goals from this study will be to document microbial interactions, virulence synergisms, characterize both acquired and active immune responses, and relate these to alterations in tissue destruction and bone resorption. The significance of this application is that clinical observations have shown the ability of oral microorganisms to translocate into the circulation and manifest systemically as endocarditis, brain/kidney/lung, and intra-abdominal infections and contributing to risks of diabetes, coronary artery disease, osteoporosis, obesity, and preterm birth. Consequently, the host response to these chronic infections must be considered as critical to general health.