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: 7960028
• 负责人: Christopher L. Pritchett
• 金额: $ 2.8万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960028
• 关键词: Attenuated; Biomedical Research; 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; Oklahoma; Pathogenesis; Poikilotherms; Protocols documentation; Rana pipiens; Research; Research Personnel; Resources; Source; Tuberculosis; United States National Institutes of Health; Vaccines; Virulence; Virulence Factors; Zebrafish; mutant; mycobacterial; pathogen

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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。由于研究结核分枝杆菌的困难，我们对分枝杆菌发病机制的了解受到严重限制。其他致病菌，如海分枝杆菌，已被用来研究分枝杆菌的致病机制。海分枝杆菌在变温动物中引起慢性消耗性疾病，也是人类的机会致病菌。已经开发了几种模型来研究海分枝杆菌感染，包括：金鱼、豹蛙和斑马鱼。海分枝杆菌使用的致病机制与结核分枝杆菌使用的致病机制相似。我们的目标是使用修改后的签名标记诱变方案与分枝杆菌发病机制的斑马鱼模型相结合来识别新的毒力决定因素。我们将使用大小不同的标签，而不是使用顺序不同的标签。这将使我们能够使用 PCR 方法来筛选突变文库，而不是使用杂交来检测标签。当前提案的具体目标是：1）构建具有不同大小标签的特征标记突变体，2）鉴定减毒突变体，3）确定海分枝杆菌中的毒力基因。我们希望确定新的毒力因子，这将有助于我们了解分枝杆菌的发病机制，并导致针对致病性分枝杆菌的新化疗药物或疫苗的开发。