Generation of a Complete Set of Precise Null Bar-Coded Deletion Mutants of Mycobacterium tuberculosis

结核分枝杆菌一整套精确空条形码缺失突变体的生成

• 批准号: 10556037
• 负责人: WILLIAM Robert JACOBS
• 金额: $ 76.45万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-14 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10556037
• 关键词: Acceleration; Alleles; Attenuated; Bacillus; Bacteriophages; Bar Codes; Biology; COVID-19 pandemic; CRISPR library; Caring; Cessation of life; Collection; Communities; Containment; DNA; Data; Developing Countries; Development; Diagnosis; Discipline; Electroporation; Engineering; Epidemic; Extreme drug resistant tuberculosis; Foundations; Fright; Gene Deletion; Gene Family; Gene Frequency; Gene Targeting; Generations; Genes; Genetic; Genome; Genotype; Goals; Growth; HIV; Immunologics; International; M. tuberculosis genome; Metabolism; Methodology; Molecular Genetics; Morbidity - disease rate; Multidrug-Resistant Tuberculosis; Mutagenesis; Mycobacteriophages; Mycobacterium smegmatis; Mycobacterium tuberculosis; Mycobacterium tuberculosis H37Rv; Nucleotides; Persons; Phenotype; Physiology; Plasmids; Process; Proteins; Protocols documentation; Publications; Quality Control; Reagent; Recombinants; Research; Research Personnel; Resources; Source; Tuberculosis; Vaccines; Virulent; chemotherapy; cost effective; genetic manipulation; genome-wide; global health; health inequalities; improved; knockout gene; manufacturing scale-up; mortality; mutant; mycobacterial; null mutation; pathogen; success; therapeutic target; therapeutically effective; therapy development; tuberculosis diagnostics; vector

Project Abstract Tuberculosis (TB) continues to be a major global health problem with 9 million new cases per year resulting in 1.7 million deaths, due in large part to the HIV epidemic and emergence of multi- and extensively drug resistant TB strains (MDR- and XDR-TB) that have confounded TB control. There will be no lasting reduction of TB morbidity and mortality without rapid and cost-effective TB diagnostics, efficacious vaccines, and shortened, well-tolerated chemotherapy, which can only be developed on the foundation of understanding the biology of the tubercle bacilli and subsequent host-pathogen interactions. The goal of this proposal is to accelerate TB research through the completion and distribution of 4,000 specialized transducing reagents to make precise null bar-coded deletion (PNBCD) mutants in every gene of M. tuberculosis. We plan to make mutants in virulent Mtb strains and mc27902, an attenuated Mtb strain that can be used under BSL2-containment. We will partner with ATCC (BEI) for distribution of these and distribution

项目摘要 结核病（TB）仍然是一个主要的全球健康问题， 每年有170万例死亡，主要是由于艾滋病毒的流行， 出现多重和广泛耐药结核菌株（MDR和XDR-TB）， 使结核病控制工作陷入困境。结核病发病率不会持久下降， 没有快速和具有成本效益的结核病诊断、有效的疫苗， 缩短的，耐受性良好的化疗，只能在基础上开发 了解结核杆菌的生物学和随后的宿主病原体 交互.该提案的目标是通过 完成并分发4，000种专用转导试剂， 在M.结核我们计划 在毒性Mtb菌株和mc 27902中产生突变体，mc 27902是一种减毒Mtb菌株， 在BSL 2控制下使用。我们将与ATCC（BEI）合作， 和分布