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GrgA:a Multifunctional Transcription Factor that Control Chlamydial Gene Expression

GrgA：控制衣原体基因表达的多功能转录因子

基本信息

批准号：
9884720
负责人：
HUIZHOU FAN
金额：
$ 23.73万
依托单位：
RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-04 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9884720
关键词：
Affinity Anti-Bacterial Agents Antibiotic Therapy Antibiotics Bacteria Bacterial RNA Binding Biology Catalytic Domain Cells ChIP-seq Chlamydia Chlamydia Infections Chlamydia genome Chlamydia trachomatis DNA DNA-Directed RNA Polymerase Defect Development Ectopic Pregnancy Environment Enzymes Escherichia coli Gene Expression Genes Genetic Transcription Genomics Goals Grant Growth Growth and Development function Heat-Shock Response High-Throughput DNA Sequencing Holoenzymes In Vitro Individual Infection Infertility Knock-out Length Medical Microbiology Pathogenicity Pelvic Inflammatory Disease Physiological Physiology Play Preventive Promoter Regions Proteins Publishing RNA Binding RNA chemical synthesis Reproductive system Research Role Scientist Sexual Transmission Sigma Factor Specificity Structure Testing Therapeutic Transcriptional Regulation Treatment Efficacy Woman Work abortion antimicrobial base biological adaptation to stress chromatin immunoprecipitation enzyme activity extracellular insight knockout gene medical attention mutant novel novel therapeutics overexpression pathogenic bacteria prevent promoter prophylactic response structural biology therapeutic target transcription factor transcriptome transcriptomics tubal infertility

项目摘要

PROJECT SUMMARY/ABSTRACT The goals of this R21 grant is to test the hypothesis that a novel Chlamydia-specific transcription factor termed GrgA controls chlamydial growth and/or development by functioning as a multifunctional protein in transcription. Chlamydia is an obligate intracellular bacterium with a unique developmental cycle. It is the number one sexually transmitted bacterial pathogen. Although mostly asymptomatic, chlamydial infection often leads to serious and long-lasting complications including (but not limited to) infertility, and pelvic inflammatory syndrome. Transcription controls chlamydial growth and pathogenicity, and is an effective therapeutic target for chlamydiae. However, current antichlamydials including transcription inhibition-based antichlamydials are not ideal therapeuticals because of their broad antibacterial spectrum. The novel transcription factor GrgA is found only in chlamydiae, and therefore represents a potentially novel and highly selective antichlamydial target. Our published work and unpublished preliminary studies suggest that GrgA plays multiple roles in transcription regulation. We propose two Specific Aims to test this hypothesis. In Aim 1, we will investigate the likelihood that GrgA facilitates assembly of chlamydial RNA polymerase. In Aim 2, we will exam the effects of GrgA gene knockout as well as GrgA overexpression on chlamydial growth, development and transcriptome expression. This research will yield insights into mechanisms that control transcription regulation in chlamydia, and may provide further rationale for targeting GrgA for therapeutic and prophylactic purposes.

项目概要/摘要 R21 资助的目标是检验一种新的衣原体特异性转录的假设称为 GrgA 的因子通过作为多功能因子来控制衣原体生长和/或发育转录中的蛋白质。衣原体是一种专性细胞内细菌，具有独特的发育周期。它是第一大性传播细菌病原体。尽管大多数无症状，但衣原体感染通常会导致严重且持久的并发症，包括（但不限于）不孕症，以及盆腔炎综合症。转录控制衣原体的生长和致病性，是衣原体的有效治疗靶点。然而，目前的抗衣原体药物（包括转录）基于抑制的抗衣原体药物由于其抗菌谱广泛，并不是理想的治疗药物。新型转录因子 GrgA 仅在衣原体中发现，因此代表了一种潜在的新型转录因子和高度选择性的抗衣原体靶标。我们已发表的工作和未发表的初步研究表明 GrgA 在转录调控中发挥多种作用。我们提出两个具体目标来测试这一点假设。在目标 1 中，我们将研究 GrgA 促进衣原体 RNA 组装的可能性聚合酶。在目标 2 中，我们将检查 GrgA 基因敲除以及 GrgA 过表达对衣原体生长、发育和转录组表达。这项研究将深入了解控制衣原体转录调控的机制，并可能提供进一步的理论依据以 GrgA 为治疗和预防目的。