Ordered gene knockout libraries for Neisseria gonorrhoeae

有序的淋病奈瑟菌基因敲除文库

• 批准号: 10437587
• 负责人: Hank S. SEIFERT
• 金额: $ 77.71万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10437587
• 关键词: Anatomy; Antibiotic Resistance; Backcrossings; Bacteria; Bar Codes; California; Case Study; Codon Nucleotides; Communities; Competence; Consensus; DNA; Development; Disease; Ensure; Gene Order; Genes; Genetic; Genetic Recombination; Genome; Gonorrhea; Grant; Human; Individual; Infection; International; Investigation; Kanamycin Resistance; Knowledge; Laboratories; Letters; Libraries; Link; Modern 1601-history; Mutate; Mutation; National Institute of Allergy and Infectious Disease; Neisseria; Neisseria gonorrhoeae; Open Reading Frames; Organism; Pathogenesis; Pathogenicity; Persons; Phylogenetic Analysis; Physiology; Population; Reporting; Research; Research Personnel; Resource Sharing; Resources; Schedule; Sexually Transmitted Agents; Sexually Transmitted Diseases; Suggestion; Uncertainty; Vaccines; Work; design; drug-resistant gonorrhea; genetic resource; human pathogen; innovation; knockout gene; meetings; mutant; pathogen; programs; resistance gene; resistance mechanism; screening; symposium; synthetic construct; transmission process; vaccine candidate

Abstract Neisseria gonorrhoeae is the sole causative agent of the sexually transmitted infection gonorrhea that is restricted to the human population. N. gonorrhoeae has co-evolved with its human host throughout all modern history and has evolved specific mechanisms of pathogenesis that relate to its mode of transmission and the anatomical sites it colonizes. Rates of gonorrhea are rising along with a rapid acquisition of antibiotic resistance. There is an urgent need to understand of the mechanisms of N. gonorrhoeae pathogenesis to develop new treatment options or vaccine candidates. N. gonorrhoeae is naturally competent for DNA transformation and is one of a few bacterial species that does not regulate competence. This resource grant will leverage the transformation competence of N. gonorrhoeae and synthetic DNA constructs to create ordered gene knockout libraries of the two most commonly used N. gonorrhoeae strains, MS11 and FA1090. These strains represent different phylogenetic clades of the bacterium. The libraries will include deletions of all genes encoding an open reading frame (ORF) that will allow the replacement of the ORF with a non-polar kanamycin resistance gene (KmR). Each KmR insertion mutant will also carry a unique random barcode. Leading researchers in the field and NIAID program officials also support this resource proposal as an important shared resource to help advance progress in this field.

抽象的 Neisseria Gonorrhoeae是性传播感染淋病的唯一病因 仅限于人口。 N. Gonorrhoeae与其人类宿主共同发展 所有现代历史，并发展了与其模式相关的发病机理的特定机制 传输及其定居的解剖位点。淋病的发生率正在上升 获得抗生素耐药性。迫切需要了解N的机制。 淋病的发病机理开发新的治疗选择或候选疫苗。 N. Gonorrhoeae 自然具有DNA转化的能力，并且是几种不符合DNA的细菌物种之一 规范能力。该资源赠款将利用N的转型能力。 淋病和合成DNA构建体以创建有序的两个基因敲除库最多 常用的淋病链球菌菌株，MS11和FA1090。这些菌株代表不同的 细菌的系统发育进化枝。库将包括所有编码的基因的删除 开放式阅读框（ORF）将允许用非极性kanamycin更换ORF 抗性基因（KMR）。每个KMR插入突变体还将携带独特的随机条形码。 该领域的主要研究人员和NIAID计划官员也支持此资源建议 一个重要的共享资源，可帮助进步该领域的进步。