Anti-adhesive prevention of Chlamydia trachomatis genital tract infection

防粘连预防沙眼衣原体生殖道感染

基本信息

批准号：
7898727
负责人：
LEE ANN CAMPBELL
金额：
$ 23.4万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-23 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7898727
关键词：
Adhesives Binding Biological Assay Body Fluids Carbohydrates Cell Culture Techniques Cell surface Cells Centers for Disease Control and Prevention (U.S.)Cervical Cervicitis Chlamydia Chlamydia trachomatis Cream Development Devices Disease Drug Formulations Ectopic Pregnancy Endometritis Epithelial Cells Excision Film Gel Genital system Glycoproteins Goals Gram&apos s stain Grant Human Immunobiology In Vitro Infection Infection prevention Infertility Inflammation Ligands Local Microbicides Lung Macaca nemestrina Mannans Mannose Methods Modeling Morbidity - disease rate Mucous Membrane Oligosaccharides Organism Outcome Ovalbumin Pelvic Inflammatory Disease Pneumonia Polysaccharides Prevention Prevention strategy Preventive Primates Public Health Reporting Research Personnel Safety Salpingitis Screening procedure Sexually Transmitted Diseases Structure Subgroup Testing Tissues United States Vaccines Vagina Woman base combat cost cytokine disorder prevention efficacy testing genital infection genital secretion global health immunogenic in vivo inflammatory marker inhibitor/antagonist major outer membrane protein mannose receptor microbial microbicide mouse model novel novel strategies obligate intracellular parasite pathogen preclinical study prevent public health relevance receptor reproductive routine Bacterial stain sugar tissue/cell culture

项目摘要

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.

描述（由申请人提供）：性传播感染（STI）对公共健康有巨大影响。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，估计美国每年有 3 至 400 万例病例。粘膜感染导致宫颈炎、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（PID）、宫外孕和不孕症。尽管发病率和成本负担很高，但目前还没有有效的疫苗。一种有前途的替代预防方法是使用局部杀菌剂，可以以凝胶、霜剂或其他制剂的形式应用于阴道内。制定预防这种专性细胞内病原体感染的有效策略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糖寡糖作为新型外用杀菌剂来预防沙眼衣原体感染的可行性。这种方法基于我们的研究，证明衣原体聚糖（一种高甘露糖寡糖）通过与宿主细胞上的甘露糖受体结合而成为附着和感染性的关键。值得注意的是，高甘露糖寡糖或去除聚糖可抑制体外细胞培养物和体内小鼠肺部感染模型的感染性。因此，我们将检验以下假设：高甘露寡糖将是沙眼衣原体生殖道感染的有效抗粘连预防方法。这将通过在生殖道感染小鼠模型中确定高甘露糖低聚糖在体外和体内抑制沙眼衣原体生殖血清型感染性的功效来在体外实现。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、宫外孕和不孕症。该提案旨在确定一种新型抗粘连预防方法的可行性，该方法可用作局部杀菌剂，以预防这种病原体的生殖道感染。