Invasion-Associated Bacterial Polymorphisms

描述(申请人提供)：牙龈卟啉单胞菌是一种侵袭性厌氧菌，与牙周组织破坏和心血管疾病有关。牙龈假单胞菌侵入高度血管化的牙龈组织，获得铁和其他营养来源。我们观察到，不同的牙龈假单胞菌菌株的侵袭能力差异高达三个数量级。这很可能是由牙龈假单胞菌基因组上存在的遗传多态所解释的。因此，我们的假设是，这种侵袭变异性反映了菌株间的基因组异质性。因此，我们的目标是使用微阵列比较基因组杂交(CGH)分析具有不同侵袭能力的牙龈假单胞菌菌株，以识别侵袭基因中与侵袭相关的细菌基因亚集。识别独特的入侵相关毒力因子将有助于更好地理解这种生物的毒力机制和遗传异质性。这种方法还可能确定侵入性细菌和宿主组织之间的串扰所涉及的部分。这些信息应该有助于开发新的明确的分子方法来治疗牙周炎。7.公共卫生意义：牙龈卟啉单胞菌是一种在牙周病和心脏病斑块中发现的细菌。这个项目的目标是更多地了解牙龈假单胞菌是如何进入人体细胞致病的。这一知识可能会让我们开发出新的、更有效的牙床和心脏疾病的治疗方法。

DESCRIPTION (provided by applicant): Porphyromonas gingivalis is an invasive anaerobe implicated in periodontal tissue destruction and cardiovascular disease. P. gingivalis invades highly vascularized gingival tissues, gaining access to iron and other nutritional sources. We have observed that the invasive ability of various P. gingivalis strains varies by as much as three orders of magnitude. This is most likely explained by genetic polymorphisms present on the P. gingivalis genome. It is thus our hypothesis that this invasion variability reflects inter-strain genomic heterogeneity. Consequently, our goal is to use microarray comparative genomic hybridization (CGH) analysis of P. gingivalis strains that have diverse invasion abilities in order to identify the invasion-associated subset of bacterial genes within the invasive genotype. Identification of unique invasion-associated virulence factors will lead to a better understanding of the putative virulence mechanisms and genetic heterogeneity of this organism. This approach will also likely identify moieties involved in cross talk between the invasive bacteria and the host tissue. Such information should facilitate the development of novel defined molecular approaches for the treatment of periodontitis. 7. Public Health Significance: Porphyromonas gingivalis is a bacterium found in gum disease and in plaques from heart disease. The goal of this project is to learn more about how P. gingivalis enters human cells to cause disease. This knowledge may allow us to develop new, more effective treatments for diseases of the gums and heart.