Mechanism and inhibitors of Chlamydia trachomatis infection of eukaryotic host cells

沙眼衣原体感染真核宿主细胞的机制及抑制剂

基本信息

批准号：
12671639
负责人：
NOGUCHI Masayoshi
金额：
$ 2.05万
依托单位：
AICHI MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

The mechanism and inhibitors of Chlamydia trachomatis (C. trachomatis) serovar L2 infection of eukaryotic host cells were studied using a tissue culture model infection system. Potent inhibition of the infectivity was observed when elementary bodies (EBs) were exposed to heparin or when HeLa 229 cells were treated with heparinase. No significant inhibition was seen the other way around. The same potent inhibition was observed when EBs were exposed to chemically 2-O-desulfated heparin (2-ODS heparin) which is composed of repeating disaccharide units of IdoA-GlcNS(6S), but not when exposed to chemically 6-O-desulfated heparin (6-ODS heparin) or completely desulfated and N-resulfated heparin (CDSNS heparin) which is composed of repeating disaccharide units of IdoA(2S)-GlcNS or IdoA-GlcNS, respectively. The inhibitory effects of 2-ODS heparin could be seen with their oligosaccharides longer than dodecasaccharides. The mutant CHO cell line, 677, which is deficient in the biosynthesis of heparan sulfate, was less sensitive to the C. trachomatis infection than wild CHO cells. F-17 cells which is deficient in 2-O-sulfation of heparan sulfate had the same sensitivity to the infection as wild CHO cells did. These data suggest that the infection of EBs to host cells results from the specific binding of ligand molecules with affinity for heparin on the EB surface to the heparan sulfate proteoglycan receptors on the host cell surface. This binding may depend on the heparan sulfate chains of host cells which are 6-O-sulfated and longer than dodecasaccharides. The 2-ODS heparin oligosaccharides may be a potential agent for the prevention of C. trachomatis infection.

利用组织培养模型感染系统研究了沙眼衣原体（C. trachomatis）血清型L2感染真核宿主细胞的机制和抑制剂。当基体 (EB) 暴露于肝素或用肝素酶处理 HeLa 229 细胞时，观察到对感染性的有效抑制。反之则没有观察到明显的抑制作用。当 EB 暴露于由 IdoA-GlcNS(6S) 重复二糖单元组成的化学 2-O-脱硫肝素（2-ODS 肝素）时，观察到相同的有效抑制作用，但当暴露于化学 6-O-脱硫肝素时，则观察不到相同的有效抑制作用。肝素（6-ODS 肝素）或完全脱硫和 N-再硫酸化肝素（CDSNS 肝素），由重复的二糖单元组成分别为 IdoA(2S)-GlcNS 或 IdoA-GlcNS。 2-ODS 肝素的抑制作用可以通过其寡糖比十二糖更长来观察到。突变型 CHO 细胞系 677 缺乏硫酸乙酰肝素的生物合成，与野生 CHO 细胞相比，对沙眼衣原体感染的敏感性较低。缺乏硫酸乙酰肝素 2-O-硫酸化的 F-17 细胞对感染的敏感性与野生 CHO 细胞相同。这些数据表明，EB对宿主细胞的感染是由于EB表面上对肝素有亲和力的配体分子与宿主细胞表面上的硫酸乙酰肝素蛋白聚糖受体的特异性结合所致。这种结合可能取决于宿主细胞的硫酸乙酰肝素链，该链是 6-O-硫酸化的并且比十二糖更长。 2-ODS 肝素寡糖可能是预防沙眼衣原体感染的潜在药物。