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Chlamydia trachomatis Secreted Effector Proteins: Infection Properties and Identification of Host Targets

沙眼衣原体分泌的效应蛋白：感染特性和宿主靶标的鉴定

基本信息

批准号：
10207380
负责人：
Gabrielle Keb
金额：
$ 0.67万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-09 至 2021-08-10
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10207380
关键词：
Alleles Attenuated Bacteria Biological Assay Biology Biotin Cells Chlamydia Infections Chlamydia trachomatis Co-Immunoprecipitations Cytolysis Defect Development Disease Drug Targeting Epithelial Fluorescence Genes Genetic Transcription Genome Growth Hela Cells Immune response Immunoprecipitation In Vitro Indirect Immunofluorescence Individual Infection Infertility Invaded Label Link LoxP-flanked allele Maintenance Mass Spectrum Analysis Membrane Modeling Molecular Molecular Chaperones Mucous Membrane Mus Mutagenesis Outcomes Research Pathogenesis Pathology Pathway interactions Phenotype Plasma Production Property Proteins Reporting Reproductive Health Research Sexually Transmitted Diseases Stains Surface Techniques Technology Time Transcript Type III Secretion System Pathway United States Vacuole Western Blotting Woman Work immunopathology in vitro Model in vivo interest mouse model mutant new technology novel marker prevent receptor tissue culture

项目摘要

Project Summary Chlamydia trachomatis is the causative agent of most commonly reported sexually transmitted disease in the United States. Disease is most severe in women and can cause detrimental effects to reproductive health, such as infertility. Establishment of an intracellular niche within non-immune cells, such as mucosal epithelium, is sufficient to drive immunopathology and disease sequela. C. trachomatis lacking both TmeA and TmeB, type III secretion system effectors, generate fewer infectious progeny in tissue culture and have significantly decreased infectivity in mice. Previous attempts to identify their individual functions utilized fluorescence- reported allelic exchange mutagenesis (FRAEM), but resulted in unclear phenotypes due to cassette-induced polar effects. Recently, I have developed floxed-cassette allelic exchange mutagenesis (FLAEM), to reverse cassette-induced polar effects and generate the first ever markerless C. trachomatis deletion mutant. I hypothesize that TmeA and TmeB are functionally related and important for establishing the inclusion, because they are co-transcribed, share a common chaperone, and are secreted into the host cell at the same time. The proposed work will utilize the novel marker-less C. trachomatis deletion mutant to determine when during chlamydial development TmeA and TmeB are important, and identify their eukaryotic host cell targets. The outcomes of this research will directly contribute to our understanding of basic C. trachomatis biology and how they use secreted effectors to establish an intracellular, which will identify potential drug targets to prevent the spread of infection to millions world-wide.

项目总结