IDENTIFICATION OF MYCOBACTERIUM MARINUM VIRULENCE GENES USING A MODIFIED STM

使用改良 STM 鉴定海分枝杆菌毒力基因

• 批准号: 7610290
• 负责人: Christopher L. Pritchett
• 金额: $ 7.85万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610290
• 关键词: Attenuated; Cessation of life; Chronic Wasting Disease; Computer Retrieval of Information on Scientific Projects Database; Development; Funding; Genes; Genus Mycobacterium; Goals; Goldfish; Grant; Health; Human; Infection; Institution; Knowledge; Lead; Libraries; Methodology; Modeling; Mutagenesis; Mycobacterium marinum; Mycobacterium tuberculosis; Pathogenesis; Poikilotherms; Polymerase Chain Reaction; Protocols documentation; Rana pipiens; Research; Research Personnel; Resources; Source; Tuberculosis; United States National Institutes of Health; Vaccines; Virulence; Virulence Factors; Zebrafish; mutant; mycobacterial; pathogen; size

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tuberculosis continues to pose a serious threat to human health with approximately 2 million deaths per annum. Our knowledge of mycobacterial pathogenesis is severely limited by the difficulties studying M. tuberculosis. Other pathogenic species, like Mycobacterium marinum, have been utilized to investigate pathogenic mechanisms of mycobacteria. Mycobacterium marinum causes a chronic, wasting disease in poikilotherms, and also is an opportunistic pathogen of humans. Several models have been developed to study M. marinum infection including: goldfish, leopard frogs, and zebrafish. The pathogenic mechanisms used by M. marinum are similar to those used by M. tuberculosis. Our goal is to identify new virulence determinants using a modified signature-tagged mutagenesis protocol in concert with the zebrafish model of mycobacterial pathogenesis. Instead of using tags that differ in sequence, we will use tags that differ in size. This will allow us to screen mutant libraries using a PCR methodology instead of using hybridizations to detect tags. The specific aims of the current proposal are: 1) construct signature-tagged mutants with different sized tags, 2) identify attenuated mutants, and 3) determine virulence genes in M. marinum. We hope to identify new virulence factors that will aid our understanding of mycobacterial pathogenesis, and lead to the development of new chemotherapeutics or vaccines against pathogenic mycobacteria.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 结核病继续对人类健康构成严重威胁，每年约有200万人死亡。结核分枝杆菌研究的困难严重限制了我们对分枝杆菌发病机制的了解。其他致病物种，如海洋分枝杆菌，已被用于研究分枝杆菌的致病机制。海洋分枝杆菌在变温动物中引起一种慢性、消耗性疾病，也是人类的一种机会性病原体。已经开发了几个模型来研究海洋分枝杆菌感染，包括：金鱼、豹蛙和斑马鱼。海洋分枝杆菌的致病机制与结核分枝杆菌的致病机制相似。我们的目标是使用一种与斑马鱼分枝杆菌致病模型相一致的改进的签名标记突变方案来识别新的毒力决定因素。我们将使用大小不同的标记，而不是使用顺序不同的标记。这将允许我们使用PCR方法来筛选突变文库，而不是使用杂交来检测标签。本方案的具体目标是：1)构建具有不同大小标签的签名标记突变体；2)鉴定减毒突变体；3)确定海洋分枝杆菌的毒力基因。我们希望发现新的毒力因子，以帮助我们了解分枝杆菌的发病机制，并导致针对致病分枝杆菌的新的化疗药物或疫苗的开发。