Anti-adhesive prevention of Chlamydia trachomatis genital tract infection

描述(申请人提供)：性传播感染(STI)对公众健康有巨大影响。沙眼衣原体是全球细菌性传播感染的主要原因，也是美国最流行的性传播疾病，据估计，美国每年有300万至400万病例。粘膜感染会导致宫颈炎症、子宫内膜炎和输卵管炎。未经治疗的感染的病理后果可能导致严重的生殖道疾病，包括盆腔炎、异位妊娠和不孕。尽管发病率和成本负担很高，但目前还没有有效的疫苗。一种有希望的替代预防方法是使用局部杀微生物剂，这种杀菌剂可以在阴道内以凝胶、乳膏或其他配方使用。开发有效的策略来预防这种专性细胞内病原体的感染的关键是防止附着和内化。在这项研究中，我们建议测试使用高甘露低聚糖作为一种新型局部杀菌剂预防沙眼衣原体感染的可行性。这种方法是基于我们的研究表明，衣原体多糖是一种高甘露糖低聚糖，通过与宿主细胞上的甘露糖受体结合，是附着和感染性的关键。值得注意的是，在体外细胞培养和体内小鼠肺部感染模型中，高甘露糖低聚糖或去除低聚糖可以抑制感染性。因此，我们将验证这样的假设，即高甘露低聚糖将是沙眼衣原体生殖道感染的有效抗粘连预防方法。这将在体外通过在生殖道感染的小鼠模型中确定高甘露糖在体外和体内抑制沙眼衣原体生殖器血清型的传染性的有效性来完成。公共卫生相关性：沙眼衣原体是美国性传播感染的主要原因，对女性造成严重后果，包括盆腔炎、宫外孕和不孕。这项建议旨在确定一种新的防粘连预防方法的可行性，该方法可用作局部杀微生物剂，以防止生殖道感染这种病原体。

DESCRIPTION (provided by applicant): Sexually transmitted infections (STIs) have a huge impact on public health. Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections globally, and is the most prevalent sexually transmitted diseases in the United State, with an estimated 3 to 4 million cases in the United States per year. Infection of the mucosa results in cervicitis, endometritis, and salpingitis. The pathological consequences of untreated infections may result in severe reproductive tract disease including pelvic inflammatory disease (PID), ectopic pregnancy and infertility. Despite the high morbidity and cost burden, there are currently no effective vaccines. A promising alternative preventive approach is the use of topical microbicides that can be applied intravaginally in a gel, cream, or other formulation. Key to the development of effective strategies for preventing infection of this obligate intracellular pathogen is to prevent attachment and internalization. In this study, we propose to test the feasibility of using high mannose oligosaccharides as a novel topical microbicide for preventing C trachomatis infection. This approach is based on our studies demonstrating that the chlamydial glycan, a high mannose oligosaccharide, is key to attachment and infectivity by binding to the mannose receptor on host cells. Significantly, high mannose oligosaccharides or removal of the glycan inhibit infectivity in vitro in cell culture and in vivo in a mouse model of lung infection. Thus, we will test the hypothesis that high mannose oligosaccharides will be an effective anti-adhesive prevention method for C. trachomatis genital tract infection. This will be accomplished in vitro by determining the efficacy of high mannose oiigosaccharides in inhibiting infectivity of C. trachomatis genital serovars in vitro and in vivo in a mouse model of genital tract infection. PUBLIC HEALTH RELEVANCE: Chlamydia trachomatis is the leading cause of sexually transmitted infection in the US with severe outcomes in women including pelvic inflammatory disease, ectopic pregnancy and infertility. This proposal seeks to determine the feasibility of a novel anti-adhesive prevention method that could be used as a topical microbicide to prevent genital tract infection with this pathogen.