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Functional Analysis of the Clp Protease Systems in Chlamydial Growth and Differentiation

Clp 蛋白酶系统在衣原体生长和分化中的功能分析

基本信息

批准号：
10501967
负责人：
Derek James Fisher
金额：
$ 25.12万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10501967
关键词：
ATP phosphohydrolase Adult Arginine Asthma Bacillus subtilis Bacteria Binding Sites Biochemical Biological Assay Biology Blindness Cell Cycle Cell physiology Cells Centers for Disease Control and Prevention (U.S.)Chlamydia Chlamydia Infections Chlamydia trachomatis Chronic ClpX protein Complex Data Dependence Developed Countries Developing Countries Development Differentiation and Growth Disease Drug Targeting Elements Ensure Essential Amino Acids Genes Genetic Genetic Techniques Genetic Transcription Genome Goals Growth Growth and Development function Healthcare Systems Heart Diseases Homeostasis Human Immunologics In Vitro Incidence Infertility Interferon Type II Lead Mediating Metabolic Molecular Chaperones Morbidity - disease rate Morphology Operon Organism Orthologous Gene Oxidation-Reduction Oxides Pathogenesis Pathway interactions Patients Pelvic Inflammatory Disease Peptide Hydrolases Peptides Phosphotransferases Pneumonia Process Protein Isoforms Proteins Proteome Proteomics Regulation Reiter Disease Reporting Respiratory Tract Infections Role Sexually Transmitted Diseases Signal Pathway Signal Transduction Stress Symptoms System Therapeutic Therapeutic Agents Trachoma Translating Translations Tryptophan Work antimicrobial biological adaptation to stress design human pathogen in vivo infection burden interest mutant normal microbiota novel novel therapeutics overexpression pathogen pathogenic bacteria phospho-L-arginine protein degradation proteostasis stem therapeutic target tmRNA tool tubal infertility

项目摘要

Project Summary: Functional analysis of the Clp Protease Systems in Chlamydial Growth and Differentiation Chlamydia is an obligate intracellular bacterial pathogen that causes a range of serious diseases in humans. In developed countries, Chlamydia trachomatis is the primary cause of bacterial sexually transmitted infections (STI). Indeed, recent reports from the Centers for Disease Control highlight the increasing incidence of STIs, with chlamydia infections consistently outpacing all other types. In developing countries, C. trachomatis is not only a significant cause of STI, but it is also responsible for the primary cause of infectious preventable blindness, trachoma. The major concern of chlamydial infections is that they are often asymptomatic and undiagnosed, which can lead to chronic sequelae. These include pelvic inflammatory disease, tubal factor infertility, and reactive arthritis for C. trachomatis. Consequently, chlamydial diseases remain a significant burden on health care systems around the world. In adapting to obligate intracellular growth, Chlamydia has significantly reduced its genome size and eliminated genes from various pathways as it relies on the host cell for its metabolic needs. This pathogen has also adapted to alternate between different functional and morphological forms during its normal growth, also referred to as its developmental cycle. These observations, combined with its obligate intracellular dependence, makes Chlamydia a difficult organism with which to work. However, recent development of genetic tools to study chlamydiae mechanistically have significantly enhanced our understanding of this pathogen. This proposal applies a combination of these new genetic techniques and classical biochemical studies to evaluate the role of conserved protease systems in chlamydial growth and pathogenesis. The hypothesis of the proposed work is that Chlamydia uses two separate protease systems to regulate its growth and transition between developmental forms as well as to respond to stress. Major goals of the proposal include (i) characterizing the function of the different protease systems both in vitro and in vivo and (ii) identifying and validating substrates of these protease systems. Results will advance our understanding of this important pathogen and lead to the design of novel therapeutic agents that are specific for Chlamydia. This in turn will allow for minimal effects on normal flora for patients receiving treatment for this highly prevalent disease.

项目总结：Clp蛋白酶系统在衣原体生长中的功能分析