Pathogenomics of Chlamydial Infection

衣原体感染的病理基因组学

• 批准号: 8745370
• 负责人: HARLAN D CALDWELL
• 金额: $ 88.71万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8745370
• 关键词: Anabolism; Antigens; Attenuated Live Virus Vaccine; Biology; Chlamydia Infections; Chlamydia trachomatis; Eye diseases; Genes; Genetic Transcription; Genital system; Glycogen; Goals; HIV; Heterophile Antigens; Immunity; Infection; Inflammation Mediators; Inflammatory; Interferon Type I; Life; Malignant neoplasm of cervix uteri; Measurable; Organism; Pathogenesis; Pathogenicity; Pathology; Plasmids; Risk Factors; Role; Serotyping; Sexually Transmitted Diseases; Signal Transduction; T-Lymphocyte; Trachoma; Vaccines; Viral; Virulence; Virulence Factors; Woman; Work; attenuation; design; gene function; immunogenicity; mutant; prevent; transmission process

Chlamydia trachomatis causes inflammatory diseases of the eye and genital tract of global importance. Its cryptic plasmid is a key virulence factor in chlamydial pathogenicity. Infections produced by plasmid-cured organisms are short-lived, resolve without measurable pathology, and paradoxically induce superior levels of protective immunity. To better understand the function of plasmid genes we made deletion mutants of all 8 plasmid genes and characterized the gene functions in plasmid biology and pathogenesis. We show that Pgp4 controls the transcription of multiple chlamydial chromosomal genes including those that function in glycogen biosynthesis and type I interferon signaling. Collectively, the findings support a role for Pgp4-regulated chromosomal genes as mediators of inflammation and modulators of T-cell immunity that offer a plausible explanation for the attenuation and superior protective immunogenicity of plasmid-deficient organisms. We will purse the use of the chlamydial plasmid to clone multiple chlamlydial ompA genes (primary serotyping and neutralization target), over express chlamydial protective T cell antigens, and express heterologous antigens from other viral and bacterial STI.

沙眼衣原体会引起眼睛和生殖道的炎症性疾病。 它的神秘质粒是衣原体致病性的关键毒力因子。 由质粒固定生物产生的感染是短暂的，没有可测量的病理，并且矛盾地诱导了优异的保护性免疫。 为了更好地了解质粒基因的功能，我们使所有8种质粒基因的缺失突变体对质粒生物学和发病机理中的基因功能进行了表征。 我们表明，PGP4控制多个衣原体染色体基因的转录，包括在糖原生物合成和I型干扰素信号传导中起作用的衣原体染色体基因。总的来说，这些发现支持PGP4调节的染色体基因作为炎症和T细胞免疫调节剂的介体，为质粒缺乏生物体的衰减和优异的保护性免疫原性提供了合理的解释。我们将使用衣原体质粒的使用来克隆多个衣原体OMPA基因（主要的血清分型和中和靶），而不是表达衣原体保护性T细胞抗原，并从其他病毒和细菌性STI中表达异源抗原。