权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Chlamydia virulence: exploitation of host N-glycosylation

衣原体毒力：利用宿主 N-糖基化

基本信息

批准号：
9390739
负责人：
LEE ANN CAMPBELL
金额：
$ 38.63万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-12-01 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9390739
关键词：
Acute Adhesives Antibiotics Architecture Bacteria Bacterial Proteins Birds Blindness Campylobacter Cardiovascular Diseases Catalytic Domain Cells Characteristics Chinese Hamster Ovary Cell Chlamydia Chlamydia Infections Chlamydia trachomatis Chlamydophila pneumoniae Chlamydophila psittaci Chronic Complex Confocal Microscopy Development Disease Ectopic Pregnancy Endoplasmic Reticulum Excision Foundations Future Genome Genomics Golgi Apparatus Grant Health Helicobacter Homologous Gene Human IGF Type 2 Receptor Immune response Immunobiology In Vitro Infection Infection prevention Infertility Integration Host Factors Intervention Laboratories Ligands Link Low income Lung Lung infections Mannose Maps Mechanics Microscopy Morbidity - disease rate Oligosaccharides Organism Pathway interactions Pattern Pelvic Inflammatory Disease Play Pneumonia Polysaccharides Prevention strategy Prevention therapy Preventive Intervention Process Proteins Proteomics Psittacosis Reporting Research Sexually Transmitted Diseases Small Interfering RNA Structure Testing Therapeutic Transferase Tube United States Vaccines Vacuole Vagina Validation Virulence Virulence Factors Western World Woman acute infection cell type chronic infection experimental study global health glycosylation in vivo inhibitor/antagonist knock-down major outer membrane protein mannose receptor metabolic profile mortality mouse model mutant novel novel strategies obligate intracellular parasite pathogen prevent public health relevance receptor recruit reproductive tract respiratory sugar trafficking

项目摘要

DESCRIPTION (provided by applicant): Chlamydial infections have significant impact on human health. Chlamydia trachomatis is the leading cause of sexually transmitted disease in the United States and preventable blindness in low income nations. In women, the consequences of untreated infection with C. trachomatis can be severe resulting in pelvic inflammatory disease, tubal factor infertility and ectopic pregnancy. Despite significant advances in understanding the immunobiology of chlamydial infection, there are no vaccines available. Although antibiotics are effective in treating acute infections, asymptomatic infection is common and chronic infections are difficult to treat. Thus, elucidating the interactions of this obligate intracellular parasite with the host is fundamental to identifying novel strategies for prevention intervention. A major research focus in our laboratory has been on chlamydial ligand/host receptor interactions. To this end, we have determined that the chlamydial glycan, which is an N- linked high mannose oligosaccharide on the major outer membrane protein (MOMP), plays a key role in attachment and infectivity through interaction with the host mannose receptor. Significantly, removal of the glycan or pretreatment with mannose oligosaccharides to interfere with attachment of the organism to the host significantly decreases infectivity and lung burden or shedding in mouse models of lung and genital tract infections, respectively. These findings support the potential for development of "anti-adhesive therapy" for prevention of infection. An alternative or complementary approach would be to prevent glycosylation of the chlamydial MOMP. The structure of the Chlamydia glycan is analogous to the N-glycans produced by the highly ordered N-glycosylation process in the host. At either the genomic or proteomic level, no chlamydial homologs have been found for the requisite proteins for N-glycosylation. Supported by these observations, the hypothesis to be tested is that the chlamydial MOMP is glycosylated by the host machinery and that Chlamydia recruits the machinery to the vacuole within the host that it resides. A corollary to this hypothesis that will be tested is that inhibitors of host N-glycosylation that inhibit chlamydial infectivity in vitro will decrease lung burden or vaginal shedding in mouse models of lung infection and genital tract infection, respectively. These studies may provide the foundation for development of future strategies to interfere with chlamydial infection.