Pathogenomics of Chlamydial Infection

沙眼衣原体引起全球重要的眼部和生殖道炎症性疾病。其隐蔽的质粒是衣原体致病的关键毒力因子。由质粒治愈的生物产生的感染是短暂的，在没有可测量的病理学的情况下消失，并且矛盾地诱导出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，并对这些基因在质粒生物学和致病机理中的功能进行了研究。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型干扰素信号转导中起作用的基因。总而言之，这些发现支持Pgp4调节的染色体基因作为炎症介质和T细胞免疫调节器的作用，这为质粒缺陷生物的衰减和优越的保护性免疫原性提供了可信的解释。我们将利用衣原体载体克隆多个衣原体OmpA基因(初步的血清学分型和中和靶点)，高效表达衣原体保护性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.