Exploration of SF3 as a Chemical Probe for Chlamydial Biology

项目摘要/摘要 这项R21拨款探索了一种名为SF3的新型化学探测器的用途，该探测器属于一个小组 一种名为选择性抗衣原体苯甲酰肼(SACBAHs)的化合物。沙眼衣原体 是头号性传播细菌病原体，占感染总人数的60% 向疾病和预防中心报告的病例。沙眼衣原体常见并发症 感染包括不孕症、流产、宫外孕和盆腔炎综合征。不幸的是，一个 尽管科学界做出了许多努力，但仍未开发出有效的疫苗 一个世纪。虽然几种广谱抗生素可以用来治疗感染，但它们都是负面的。 影响有益的微生物区系，并可能增加无关病原体产生抗生素耐药性的风险。 此外，目前的治疗方法临床治疗失败是很常见的。显然有必要发展 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SACBAHs是一种新型的抗衣原体药物。SACBAHs展示了几个重要的 特点。首先，它们能有效地抑制衣原体的生长。第二，它们不会影响宿主细胞 在显示完全抑制衣原体生长的浓度下生长。第三，它们不会影响 有益的乳酸菌生长，在大多数育龄妇女的阴道微生物区系中占主导地位。 我们的初步研究表明，SACBAHs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。我们将在以下位置确定SF3如何影响衣原体转录 无论是细胞水平还是分子水平。

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.