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

• 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
• 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

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.

项目总结/摘要 这项R21资助探索了一种名为SF 3的新型化学探针的实用性，SF 3属于一组 称为选择性抗衣原体苄叉酰腙（SACBAH）的化合物。沙眼衣原体 是性传播的头号细菌病原体，占感染总数的60 向疾病和预防中心报告的病例。C的常见并发症沙眼衣原体 感染包括不孕症、流产、宫外孕和盆腔炎综合症。不幸的是， 尽管科学界作出了许多努力，但仍有待开发有效的疫苗。 一个世纪虽然几种广谱抗生素可用于治疗感染，但它们对 影响有益的微生物群，并可能增加不相关病原体的抗生素耐药性风险。 此外，当前疗法的临床治疗失败是常见的。显然需要发展 选择性抑制剂，并探讨其治疗和预防衣原体感染的机制。 我们的研究小组已经确定SACBAH作为新的antichlamydiales。SACBAH展示了几个重要的 特色首先，它们对衣原体生长有效。第二，它们不影响宿主细胞 在显示衣原体生长完全抑制的浓度下生长。第三，不影响 有益乳酸杆菌的生长，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SF 3如何影响衣原体转录， 细胞和分子水平。