Exploration of SF3 as a Chemical Probe for Chlamydial Biology

SF3 作为衣原体生物学化学探针的探索

基本信息

批准号：
10043281
负责人：
HUIZHOU FAN
金额：
$ 19.52万
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：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10043281
关键词：
Affect Age Antibiotic Resistance Antibiotics Bacteria Bacterial Infections Binding Biology Calorimetry Case Study Catalytic Domain Cells Characteristics Chemicals Chlamydia Chlamydia Infections Chlamydia trachomatis Circular Dichroism Clinical Treatment Communities DNA DNA-Directed RNA Polymerase Defect Development Dissociation Ectopic Pregnancy Environment Exhibits Genes Genetic Transcription Glycine Goals Grant Growth Growth and Development function Holoenzymes In Vitro Infection Infertility Interferometry Knowledge Lactobacillus Lead Mediating Medical Microbiology Molecular Molecular Conformation Mutation Pelvic Inflammatory Disease Prevention Preventive Promoter Regions Proteins RNA RNA chemical synthesis Research Resistance Risk Role Scientist Sexual Transmission Sigma Factor Structure Testing Therapeutic Titrations Transcriptional Activation Transcriptional Regulation Treatment Failure Vaccines Variant Woman abortion antimicrobial biophysical chemistry cell growth disorder prevention extracellular in vivo inhibitor/antagonist microbiota mutant negative affect novel novel therapeutics overexpression pathogen pathogenic bacteria prevent reproductive structural biology transcription factor transcriptomics vaginal microbiota

项目摘要

PROJECT SUMMARY/ABSTRACT This R21 grant explores the utilities of a novel chemical probe termed SF3, which belongs to a group of compounds termed selective antichlamydial benzal acylhydrazones (SACBAHs). Chlamydia trachomatis is the number one sexually transmitted bacterial pathogen, which accounts for 60% of the total infected cases reported to the Centers for Diseases and Prevention. Common complications from C. trachomatis infection include infertility, abortion, ectopic pregnancy and pelvic inflammatory syndrome. Unfortunately, an effective vaccine has yet to be developed despite numerous efforts by the scientific community over half of a century. Although several broad-spectrum antibiotics can be used to treat the infection, they negatively affect the beneficial microbiota, and may increases the risk of antibiotic resistance in unrelated pathogens. In addition, clinical treatment failure with current therapies is common. There is a clear need to develop selective inhibitors and investigate their mechanisms for treatment and prevention of chlamydial infection. Our research group has identified SACBAHs as novel antichlamydials. SACBAHs exhibit several important characteristics. First, they are effective against chlamydial growth. Second; they do not affect host cell growth at concentrations that show complete inhibition of chlamydial growth. Third, they do not affect the growth of beneficial lactobacilli, which dominate the vaginal microbiota in most reproductive-age women. Our preliminary studies suggest that SACBAHs inhibit chlamydiae by interfering with the function of the Chlamydia-specific transcription factor GrgA. We will determine how SF3 affects chlamydial transcription at both the cellular and molecular levels.

项目概要/摘要这项 R21 拨款探索了一种名为 SF3 的新型化学探针的实用性，该探针属于一个小组称为选择性抗衣原体苯亚酰腙（SACBAH）的化合物。沙眼衣原体是排名第一的性传播细菌病原体，占感染总数的60% 向疾病与预防中心报告病例。沙眼衣原体的常见并发症感染包括不孕、流产、宫外孕和盆腔炎综合症。不幸的是，一个尽管科学界付出了巨大努力，但仍有一半以上的人尚未研制出有效的疫苗一个世纪。虽然几种广谱抗生素可用于治疗感染，但它们对影响有益微生物群，并可能增加无关病原体产生抗生素耐药性的风险。此外，当前疗法的临床治疗失败也很常见。有明确的发展需求选择性抑制剂并研究其治疗和预防衣原体感染的机制。我们的研究小组已将 SACBAH 确定为新型抗衣原体药物。 SACBAH 展示了几个重要的特征。首先，它们能有效抑制衣原体的生长。第二;它们不影响宿主细胞在完全抑制衣原体生长的浓度下生长。第三，不影响有益乳酸菌的生长，在大多数育龄妇女的阴道微生物群中占主导地位。我们的初步研究表明，SACBAH 通过干扰衣原体的功能来抑制衣原体。衣原体特异性转录因子 GrgA。我们将确定 SF3 如何影响衣原体转录细胞和分子水平。