Addressing genetic tractability and species-specific infection biology in Chlamydia pneumoniae

解决肺炎衣原体的遗传易处理性和物种特异性感染生物学

• 批准号: 10571366
• 负责人: KENNETH A FIELDS
• 金额: $ 22.95万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-07 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10571366
• 关键词: Acceleration; Acute; Address; Alleles; Biology; Bronchitis; Cell Separation; Cells; Cellular biology; Chlamydia; Chlamydia trachomatis; Chlamydophila pneumoniae; Communities; Comparative Study; Complement; Data; Development; Disease; Ectopic Expression; Endocytosis; Engineering; Epithelial Cells; Epitopes; Exhibits; Filopodia; Foundations; Future; Gene Deletion; Gene Duplication; Gene Expression; Genes; Genetic; Genetic Techniques; Genital; Genitalia; High Prevalence; Human; Infection; Inflammatory; Invaded; Light; Maintenance; Mediating; Molecular; Mucous Membrane; Mutagenesis; Pathogenesis; Pathogenicity; Phagocytes; Phenotype; Plasmids; Prevalence; Probability; Process; Proteins; Recruitment Activity; Research; Respiratory Disease; Respiratory Tract Infections; Reverse engineering; Role; Sinusitis; System; Techniques; Technology; Work; cell type; chronic infection; community acquired pneumonia; constitutive expression; design; efficacy testing; expression vector; gene product; genetic manipulation; human pathogen; inducible gene expression; intracellular parasitism; member; mutant; new technology; novel strategies; obligate intracellular parasite; pathogen; protein function; receptor mediated endocytosis; recruit; respiratory pathogen; seropositive; sorting nexins; tissue tropism; trafficking; vector

ABSTRACT Chlamydia species represent a paradigm for understanding successful obligate intracellular parasitism. While C. trachomatis and C. pneumoniae are both prevalent human pathogens, C. pneumoniae respiratory infections are likely most common. Acute C. pneumoniae infections manifest as community acquired pneumonia, bronchitis, and sinusitis while additional inflammatory sequelae are associated with chronic infection. Advances in genetic tractability have facilitated considerable progress in characterizing C. trachomatis pathogenesis. Unfortunately, similar progress has lagged for C. pneumoniae, leading to a paucity in details regarding molecular mechanisms of infection and precluding informative approaches leveraging comparative studies. To overcome this barrier, we will engineer plasmid systems enabling allelic replacement and ectopic gene expression for C. pneumoniae. These new technologies will be applied in proof-of-principle studies to address functional aspects manifested by a pair of divergent type III secreted effectors employed by C. pneumoniae to manipulate host cell biology. At the end of these studies, we will have established new approaches that will benefit the entire Chlamydia research community and advance the understanding of how chlamydial species have evolved to accomplish common developmental requirements.

摘要 衣原体代表了一个范例，了解成功的专性细胞内 寄生而C.沙眼衣原体和沙眼衣原体。pneumoniae是两种流行的人类病原体，C. 肺炎呼吸道感染可能是最常见的。急性C。肺炎感染 表现为社区获得性肺炎、支气管炎和鼻窦炎， 炎症后遗症与慢性感染有关。遗传易处理性研究进展 已经促进了C.沙眼发病机制 不幸的是，类似的进展在C。肺炎，导致缺乏细节 关于感染的分子机制和排除信息化的方法， 比较研究为了克服这一障碍，我们将设计质粒系统， 替换和异位基因表达。肺炎。这些新技术将 应用于原理验证研究，以解决一对 趋异的III型分泌的效应物由C.操纵宿主细胞 生物学在这些研究结束时，我们将建立新的方法， 整个衣原体研究界，并促进了解衣原体如何 物种已经进化到满足共同的发展需求。