Developing genetic transformation system in veillonellae

开发韦永菌遗传转化系统

• 批准号: 8231763
• 负责人: FENGXIA QI
• 金额: $ 37万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-22 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8231763
• 关键词: Adult; Affect; Antibiotics; Bacteria; Biology; Carbon; Characteristics; Chemicals; Child; Clinical; Clinical Research; Cloning Vectors; Communities; DNA; Dental; Dental Plaque; Dental caries; Developed Countries; Development; Disease; Disease Management; Ecology; Economic Burden; Environment; Epidemiologic Studies; Escherichia coli; Etiology; Genetic; Genetic Transformation; Gnotobiotic; Goals; Grant; Health; Health Benefit; Human; Knowledge; Laboratories; Lactic acid; Lesion; Life; Methylation; Microbial Biofilms; Molecular Epidemiology; Morbidity - disease rate; Mouth Diseases; Mutagenesis; Mutation; Nature; Oral; Oral cavity; Oral health; Organism; Pathogenesis; Periodontitis; Physiology; Plasmids; Play; Preparation; Prevention; Probiotics; Process; Production; Protocols documentation; Publishing; Rattus; Replicon; Reporting; Research; Research Personnel; Role; Series; Shuttle Vectors; Source; Streptococcus mutans; System; Temperature; Testing; Vaccination; Veillonella; Veillonella parvula; Virulence; Virulence Factors; Work; base; disorder prevention; epidemiology study; genetic manipulation; homologous recombination; improved; interest; member; microorganism; mutant; novel strategies; oral biofilm; pathogen; prevent; social; sugar; suicide vector; tool; vector

DESCRIPTION (provided by applicant): Dental caries and periodontitis are two most prevalent diseases of mankind. Although not life threatening, their morbidity continues to imposed a significant social and economic burden. The polymicrobial nature of these diseases makes them difficult to cure, and even more challenging for prevention using conventional means such as vaccination. Holistic or probiotic approaches could offer health benefits only with a deeper understanding of the inner workings of the dental biofilm community as well as their relationships with the host. Veillonella species are consistently found to be associated with dental caries and potentially periodontitis, and are speculated to contribute significantly to dental biofilm development and pathogenesis. However, due to the lack of a genetic manipulation system in this group of bacteria, our knowledge about their role in health and disease is limited at best. This project aims to establish a robust Veillonella genetic transformation system. In the first grant period, we have succeeded in obtaining the first true transformant in this genus using V. parvula strain PK1910. The current project continues the previous studies by improving transformation efficiency, constructing shuttle vectors, and creating a transformation recipient strain. Completion of these studies will establish a robust genetic transformation system for veillonellae, which will provide researchers the tools required to study Veillonella biology, physiology, ecology, and virulence under controlled laboratory conditions. PUBLIC HEALTH RELEVANCE: Dental caries and periodontitis are two most prevalent diseases of mankind, affecting the majority of children and adults, respectively, even in developed countries like the U.S. The polymicrobial etiology of these diseases makes them difficult to cure, and even more challenging for prevention through vaccination. Holistic or probiotic approaches based on understanding the ecology of the microorganisms in the dental plaque could provide viable options for disease prevention and management. This project aims to develop a genetic tool to study the biology, physiology, ecology and pathogenesis of a group of important bacteria (veillonellae) in the dental plaque, so that novel approaches can be developed for disease prevention.

描述（申请人提供）：龋齿和牙周炎是人类最常见的两种疾病。虽然不危及生命，但其发病率继续造成重大的社会和经济负担。这些疾病的多微生物性质使其难以治愈，并且对于使用常规手段如疫苗接种进行预防更具挑战性。整体或益生菌方法只有在更深入地了解牙齿生物膜群落的内部运作以及它们与宿主的关系的情况下才能提供健康益处。韦荣球菌属的物种一直被发现与龋齿和潜在的牙周炎，并推测显着贡献的牙齿生物膜的发展和发病机制。然而，由于这组细菌缺乏遗传操作系统，我们对它们在健康和疾病中的作用的了解充其量是有限的。本项目旨在建立一个强大的韦荣氏球菌遗传转化系统。在第一个授权期，我们成功地获得了该属的第一个真正的菌株，使用V.parvula菌株PK 1910。本项目在前期研究的基础上，通过提高转化效率、构建穿梭载体、构建转化受体菌株等方法，继续开展转化研究。这些研究的完成将为韦荣球菌建立一个强大的遗传转化系统，这将为研究人员提供在受控实验室条件下研究韦荣球菌生物学，生理学，生态学和毒力所需的工具。 公共卫生关系：龋齿和牙周炎是人类最流行的两种疾病，分别影响大多数儿童和成人，即使在美国等发达国家也是如此。这些疾病的多微生物病因使其难以治愈，通过疫苗接种进行预防更具挑战性。基于了解牙菌斑中微生物生态的整体或益生菌方法可以为疾病预防和管理提供可行的选择。本项目旨在开发一种基因工具，研究牙菌斑中一组重要细菌（韦荣氏菌）的生物学、生理学、生态学和发病机制，从而开发预防疾病的新方法。