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.

沙眼衣原体引起全球性的眼部和生殖道炎症性疾病。 其隐蔽质粒是衣原体致病性的关键毒力因子。 由质粒治愈的生物体产生的感染是短暂的，在没有可测量的病理学的情况下即可消退，并且矛盾的是诱导了上级水平的保护性免疫。 为了更好地了解质粒基因的功能，我们制作了所有8个质粒基因的缺失突变体，并表征了这些基因在质粒生物学和发病机制中的功能。 我们发现，Pgp 4控制多个衣原体染色体基因的转录，包括那些在糖原生物合成和I型干扰素信号传导的功能。总的来说，这些发现支持Pgp 4调节的染色体基因作为炎症介质和T细胞免疫调节剂的作用，为质粒缺陷生物体的衰减和上级保护性免疫原性提供了合理的解释。我们将寻求使用衣原体质粒克隆多个衣原体ompA基因（主要血清分型和中和靶），过表达衣原体保护性T细胞抗原，并表达来自其他病毒和细菌STI的异源抗原。