Interactions Between Oral Pathogens and Vascular Cells

口腔病原体与血管细胞之间的相互作用

• 批准号: 7932539
• 负责人: Ann Progulske-Fox
• 金额: $ 18.27万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-22 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932539
• 关键词: Address; Adhesions; Adult; Apoptosis; Atherosclerosis; Bacteria; Bacterial Adhesins; Basic Science; Biological Sciences; Blast Cell; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cell Survival; Cells; Cessation of life; Collection; Comparative Genomic Analysis; Coronary artery; DNA Sequence; Data; Databases; Defect; Developed Countries; Developing Countries; Development; Diagnostic tests; Economics; Endothelial Cells; Funding; Gene Structure; Genes; Genome; Human; Infection; Invaded; Investigation; Knowledge; Location; Low Birth Weight Infant; Membrane Microdomains; Modeling; Molecular; Molecular Profiling; Names; Oral; Oral cavity; Orthologous Gene; Pathway interactions; Periodontal Diseases; Periodontitis; Physiological; Porphyromonas gingivalis; Prevention strategy; Property; Proteins; Reading; Relative (related person); Research; Role; Site; Sorting - Cell Movement; Structure; Systemic disease; Technology; Virulence Factors; base; cell type; cost; gene function; genome sequencing; human tissue; mutant; oral pathogen; parent grant; pathogen; premature; programs; psychologic; response; tool; trafficking; uptake

DESCRIPTION (provided by applicant): Porphyromonas gingivalis is the major etiological agent of adult periodontitis. Although well established as a periodontal pathogen, it has more recently been recognized that P. gingivalis may have an important role in systemic disease, including cardiovascular diseases, prematurity and low birth weight. Cardiovascular diseases are a heterogeneous group of conditions that are the leading cause of death in developed countries. The economic losses and psychological repercussions caused by this pathogen are thus potentially enormous. During the past several years, we have investigated the pathogenic properties of P. gingivalis, focusing on its interactions with and invasion of human tissues, including coronary artery endothelial cells. However, the availability of the whole genome sequence of only one strain of P. gingivalis has hampered our research effort. Many factors suggest that investigation of other P. gingivalis strains should be pursued since strains are phenotypically and genotypically heterogeneous with regards to certain virulence factors including relative host cell invasive abilities. Consequently, this submission is requesting funding as a supplement to our recently funded competitive renewal (DE13545) to sequence and annotate the genomes of P. gingivalis strains 381, 33277, A7436, and AJW4, followed by comparative genomic analysis. Genome sequences will be determined using a new, cost-efficient, and massively parallel DMA sequencing technology developed by 454 Life Sciences (Branford, CT). Genome assembly will be supplemented with up to 1x genome coverage using paired-end Sanger DNA sequencing reads. Gene location and structures will be predicted using FGENESB. Gene function and names will be assigned to predicted gene structures based on homology searches of public gene data. Pairwise genome comparisons and multiple genome comparisons will be performed to identify orthologs that are conserved among these five genomes as well as unique genes. Genes that are missing from these genomes will also be determined. BLAST searches, MUMmer programs and VISTA tools will be used for these purposes. For all predicted proteins, a HMMER PFAM search will be conducted to detect functional domains. The availability of four additional whole genome sequences of P. gingivalis in public databases would facilitate basic research, including that of the parent grant to this supplemental application, and more rapid development of diagnostic tests, and treatment, and prevention strategies.

描述（由申请人提供）：牙龈卟啉单胞菌是成人牙周炎的主要病原体。虽然牙龈卟啉单胞菌是一种公认的牙周病原体，但最近人们认识到牙龈卟啉单胞菌可能在全身性疾病中发挥重要作用，包括心血管疾病、早产和低出生体重。心血管疾病是一组异质性疾病，是发达国家的主要死亡原因。因此，这种病原体造成的经济损失和心理影响可能是巨大的。在过去的几年中，我们研究了牙龈卟啉单胞菌的致病特性，重点是它与人体组织的相互作用和侵袭，包括冠状动脉内皮细胞。然而，只有一株牙龈卟啉单胞菌的全基因组序列的可用性阻碍了我们的研究工作。许多因素表明，应继续研究其他牙龈卟啉单胞菌菌株，因为菌株在某些毒力因子（包括相对宿主细胞侵袭能力）方面具有表型和基因型异质性。因此，本次提交申请作为我们最近资助的竞争性更新（DE 13545）的补充资金，对牙龈卟啉单胞菌菌株381、33277、A7436和AJW4的基因组进行测序和注释，然后进行比较基因组分析。基因组序列将使用454 Life Sciences（Branford，CT）开发的新的、具有成本效益的大规模并行DMA测序技术来确定。将使用配对末端桑格DNA测序读数，以高达1x的基因组覆盖率补充基因组组装。将使用FGENESB预测基因位置和结构。基因功能和名称将被分配到预测的基因结构的基础上同源性搜索的公共基因数据。将进行成对基因组比较和多基因组比较，以鉴定这五个基因组中保守的直系同源物以及独特基因。这些基因组中缺失的基因也将被确定。BLAST检索、MUMmer程序和VISTA工具将用于这些目的。对于所有预测的蛋白质，将进行HMMER PFAM搜索以检测功能结构域。在公共数据库中提供另外四个牙龈卟啉单胞菌全基因组序列将促进基础研究，包括对该补充申请的母基金的研究，以及更快地开发诊断测试、治疗和预防策略。