Mutagenesis in Chlamydia trachomatis via allelic exchange

沙眼衣原体通过等位基因交换进行诱变

基本信息

批准号：
9215637
负责人：
KENNETH A FIELDS
金额：
$ 18.81万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-08 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9215637
关键词：
Acute Disease Alleles Biology Cells Chemicals Chlamydia Chlamydia Infections Chlamydia trachomatis Chronic Disease Communities Complement Complex Data Development Dissection Dominant-Negative Mutation Ectopic Expression Epithelial Cells Essential Genes Gene Deletion Gene Silencing Gene Targeting Generations Genes Genetic Genome Goals Growth Health Human Infection Insertional Mutagenesis Investigation Learning Methods Microbiology Molecular Mutagenesis Pathogenesis Pharmacology Prevalence Protein Secretion Proteins RNA Interference Research Role Sexually Transmitted Diseases Suicide System Techniques Type III Secretion System Pathway United States Virulence Work base chemical genetics gene product genetic approach genetic manipulation inducible gene expression inhibitor/antagonist link protein loss of function member mutant new technology novel novel strategies null mutation obligate intracellular parasite pathogen protein function protein protein interaction public health relevance socioeconomics success suicide vector tool vector

Acute Disease Alleles Biology Cells Chemicals Chlamydia Chlamydia Infections Chlamydia trachomatis Chronic Disease Communities Complement Complex Data Development Dissection Dominant-Negative Mutation Ectopic Expression Epithelial Cells Essential Genes Gene Deletion Gene Silencing Gene Targeting Generations Genes Genetic Genome Goals Growth Health Human Infection Insertional Mutagenesis Investigation Learning Methods Microbiology Molecular Mutagenesis Pathogenesis Pharmacology Prevalence Protein Secretion Proteins RNA Interference Research Role Sexually Transmitted Diseases Suicide System Techniques Type III Secretion System Pathway United States Virulence Work base chemical genetics gene product genetic approach genetic manipulation inducible gene expression inhibitor/antagonist link protein loss of function member mutant new technology novel novel strategies null mutation obligate intracellular parasite pathogen protein function protein protein interaction public health relevance socioeconomics success suicide vector tool vector

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项目摘要

DESCRIPTION (provided by applicant): Chlamydia trachomatis represents a significant health concern in the United States. A substantial burden exists due to the prevalence and the combined health and socioeconomic impact of acute and chronic disease. Chlamydiae are obligate intracellular parasites that undergo a complex developmental cycle. All Chlamydia species express a type III secretion system (T3SS), and based on analogy with other T3SS-expressing pathogens, this mechanism likely contributes significantly to overall pathogenesis. Although definitive association of T3S with chlamydial virulence has proven difficult, the newly-acquired ability to genetically manipulate chlamydiae has opened new doors for progress. We present preliminary data describing the first ever Chlamydia-specific suicide vector and propose to leverage this new approach to target T3SS genes for inactivation. Specifically we will further develop the suicide vector system and directly create null mutations in specific T3S effector genes. We also propose approaches to conditionally inactivate T3S capability. At the end of these studies, we will have established molecular tools that will benefit the entire Chlamydia research community. In addition, we will gain a better understanding of how the T3SS contributes to chlamydial virulence.

描述（由适用提供）：沙眼衣原体代表了美国的重大健康问题。由于急性和慢性疾病的健康状况以及健康和社会经济的综合影响，存在大量燃烧。衣原体是经历复杂发育周期的义务细胞内寄生虫。所有衣原体物种都表达了III型分泌系统（T3SS），并基于与其他表达T3SS的病原体的类比，这种机制可能对整体发病机理有很大贡献。尽管事实证明，T3与衣原体病毒的确定关联已被证明很困难，但新获得的基因操纵衣原体的能力为进步开辟了新的大门。我们提供了初步数据，描述了有史以来第一个特定衣原体的自杀载体，并提出了利用这种新方法将T3SS基因靶向灭活的建议。具体而言，我们将进一步开发自杀矢量系统，并直接在特定T3S效应子基因中创建无效突变。我们还提出了有条件灭活T3S能力的方法。在这些研究结束时，我们将建立分子工具，以使整个衣原体研究界受益。此外，我们将更好地了解T3SS对衣原体病毒的贡献。