Pathogenomics of Chlamydial Infection

沙眼衣原体引起眼睛和生殖道的炎症性疾病，具有全球重要性。其隐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的情况下消退，并且矛盾地诱发了更高水平的保护性免疫。为了更好地了解质粒基因的功能，我们对所有8个质粒基因进行了缺失突变，并对其在质粒生物学和发病机制中的功能进行了表征。我们发现Pgp4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型干扰素信号传导中起作用的基因。总的来说，这些发现支持pgp4调节的染色体基因作为炎症介质和t细胞免疫调节剂的作用，这为质粒缺陷生物体的衰减和优越的保护性免疫原性提供了合理的解释。我们将利用衣原体质粒克隆多个衣原体ompA基因（初级血清分型和中和目标），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。

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.