Anti-adhesive prevention of Chlamydia trachomatis genital tract infection

描述（由申请人提供）：性传播感染（STI）对公共卫生有巨大的影响。沙眼衣原体是全球细菌性性传播感染的主要原因，也是美国最流行的性传播疾病，估计美国每年有300万至400万例。粘膜感染可引起宫颈炎、尿道炎和输卵管炎。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（PID），异位妊娠和不孕症。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，可以在凝胶，乳膏或其他制剂中阴道内应用。预防这种专性细胞内病原体感染的有效策略的发展关键是防止附着和内化。在这项研究中，我们建议测试的可行性，使用高甘露寡糖作为一种新的局部杀微生物剂，用于预防沙眼衣原体感染。这种方法是基于我们的研究，证明衣原体聚糖，高甘露糖寡糖，是通过结合宿主细胞上的甘露糖受体的附着和感染性的关键。值得注意的是，高甘露糖寡糖或聚糖的去除在体外细胞培养中和体内肺部感染小鼠模型中抑制感染性。因此，我们将测试高甘露寡糖将是一种有效的抗粘附预防方法的假设。沙眼生殖道感染这将在体外通过测定高甘露糖寡糖在抑制C.在生殖道感染的小鼠模型中体外和体内检测沙眼衣原体生殖器血清型。公共卫生相关性：在美国，沙眼衣原体是性传播感染的主要原因，对妇女造成严重后果，包括盆腔炎、异位妊娠和不孕症。该提案旨在确定一种新的抗粘附预防方法的可行性，该方法可用作局部杀微生物剂以预防该病原体的生殖道感染。

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.