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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的衣原体物种代表了理解成功的细胞内的范式寄生。而C. c. trachomatis和C.肺炎都是普遍的人类病原体。肺炎呼吸道感染可能是最常见的。急性肺炎C.肺炎感染表现为社区获得的肺炎，支气管炎和鼻窦炎，而另外炎性后遗症与慢性感染有关。遗传性障碍的进步在表征沙眼发病机理的表征方面取得了可观的进展。不幸的是，类似的进展落后于肺炎梭菌，导致细节稀少关于感染的分子机制和缺乏提供信息的方法比较研究。为了克服这一障碍，我们将设计质粒系统以实现等位基因肺炎梭菌的替代和异位基因表达。这些新技术将是应用于原则研究，以解决一对的功能方面 C.肺炎用来操纵宿主细胞的Divergent III型分泌效应子生物学。在这些研究结束时，我们将建立新的方法，将受益整个衣原体研究社区，并提高人们对衣原体的理解物种已经发展为达到共同的发展要求。