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，新增感染人数达 900 万 每年导致 170 万人死亡，这在很大程度上是由于艾滋病毒流行和 多重耐药和广泛耐药结核菌株（MDR-和XDR-TB）的出现 混淆了结核病控制。结核病发病率不会持久降低 如果没有快速且具有成本效益的结核病诊断、有效的疫苗和 缩短时间、耐受性良好的化疗，只能在此基础上开发 了解结核杆菌和随后的宿主病原体的生物学 互动。该提案的目标是通过以下方式加速结核病研究： 完成并分发4,000种专业转导试剂，以确保精准 结核分枝杆菌每个基因中都存在无效条形码缺失（PNBCD）突变体。我们计划 在强毒力 Mtb 菌株和 mc27902 中产生突变体，mc27902 是一种减毒 Mtb 菌株，可 在 BSL2 遏制下使用。我们将与 ATCC (BEI) 合作分发这些 和分布