Gallegos Karen M, Taylor Christopher R, Rabulinski Daniel J, Del Toro Rosalinda, Girgis Danielle E, Jourha Dapinder, Tiwari Vaibhav, Desai Umesh R, Ramsey Kyle H
Department of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL, United States.
Department of Dermatology, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado - Anschutz Medical Campus, Aurora, CO, United States.
Front Microbiol. 2019 Jan 16;9:3269. doi: 10.3389/fmicb.2018.03269. eCollection 2018.
is the most frequently reported sexually transmitted bacteria causing 2.9 million infections annually in the United States. Diagnosis, treatment, and sequelae of chlamydial disease cost billions of dollars each year in the United States alone. Considering that a heparin sulfate-like cell surface receptor is involved in infections, we reasoned that sulfated and sulfonated mimics of heparin sulfate would be useful in topical prophylactic prevention of . In this study, we tested a small, synthetic sulfated agent sulfated pentagalloyl glucoside (SPGG) and three synthetic sulfonated polymers PSS and SPS with average molecular weight in the range of 11 to 1000 kDa for inhibition against . Infection of HeLa cells with or in the presence of increasing concentrations of SPGG or sulfonated polymers were quantified by immunofluorescence of inclusions. To determine whether pre-treatment of SPGG inhibits infection of , HeLa monolayers were incubated with SPGG-containing media, and then infected with . Our results show that SPGG pre-treatment inhibits infection in a dose-dependent manner. In addition, we further determined if SPGG treatment has an inhibitory effect during infection, therefore cell monolayers were infected with in the concurrent presence of SPGG. Our results show that SPGG inhibits infection with an IC at 10 μg/ml levels. We also tested the inhibitory effect of synthetic polymers PSS and SPS against and found inhibition of and infections with IC ranging from 0.3 to 0.8 μg/ml. SPGG, PSS, and SPS inhibit formation of inclusions in a concentration-dependent manner. For evaluation of efficacy of the most effective agent in blocking , SPGG, we intravaginally pre-treated mice with SPGG before infection with . Cervical swabs were collected post-infection to quantify inclusions . Our data show that the SPGG-treated group has a statistically significant reduction of infection compared to the no-treatment control. Overall, our results show that SPGG could serve as a promising topical inhibitor for preventing infection.
是最常报告的性传播细菌，在美国每年导致290万例感染。仅在美国，衣原体疾病的诊断、治疗和后遗症每年就花费数十亿美元。考虑到一种硫酸乙酰肝素样细胞表面受体参与了感染过程，我们推测硫酸乙酰肝素的硫酸化和磺化模拟物可用于衣原体感染的局部预防性预防。在本研究中，我们测试了一种小的合成硫酸化剂硫酸化五倍子酰葡萄糖（SPGG）以及三种平均分子量在11至1000 kDa范围内的合成磺化聚合物PSS和SPS对衣原体感染的抑制作用。通过包涵体的免疫荧光定量在不同浓度的SPGG或磺化聚合物存在下，用衣原体或沙眼衣原体感染HeLa细胞的情况。为了确定SPGG预处理是否能抑制沙眼衣原体感染，将HeLa单层细胞与含SPGG的培养基孵育，然后用沙眼衣原体感染。我们的结果表明，SPGG预处理以剂量依赖的方式抑制沙眼衣原体感染。此外，我们进一步确定SPGG处理在感染期间是否具有抑制作用，因此在同时存在SPGG的情况下用沙眼衣原体感染细胞单层。我们的结果表明，SPGG在10μg/ml水平时以IC抑制沙眼衣原体感染。我们还测试了合成聚合物PSS和SPS对沙眼衣原体和性病淋巴肉芽肿衣原体的抑制作用，发现对沙眼衣原体和性病淋巴肉芽肿衣原体感染的抑制作用，IC范围为0.3至0.8μg/ml。SPGG、PSS和SPS以浓度依赖的方式抑制包涵体的形成。为了评估最有效药物在阻断沙眼衣原体感染方面的疗效，我们在感染沙眼衣原体之前用SPGG对小鼠进行阴道内预处理。感染后收集宫颈拭子以定量包涵体。我们的数据表明，与未处理的对照组相比，SPGG处理组的感染率有统计学意义的降低。总体而言，我们的结果表明，SPGG可作为预防沙眼衣原体感染的一种有前景的局部抑制剂。
