Mechanism and inhibitors of Chlamydia trachomatis infection of eukaryotic host cells

采用组织培养模型感染系统，研究了沙眼衣原体血清型L2感染真核宿主细胞的机制和抑制因子。当初等体（EBs）暴露于肝素或HeLa 229细胞用肝素酶处理时，观察到有效的传染性抑制。反之则没有明显的抑制作用。当EBs暴露于由IdoA-GlcNS（6S）的重复双糖单元组成的化学2- o -去硫肝素（2-ODS肝素）时，观察到同样有效的抑制作用，而暴露于化学6- o -去硫肝素（6-ODS肝素）或由IdoA(2S)-GlcNS或IdoA-GlcNS的重复双糖单元组成的化学6- o -去硫肝素（CDSNS肝素）时则没有。2-ODS肝素的抑制作用表现在其寡糖比十二糖长。突变型CHO细胞系677缺乏硫酸肝素的生物合成，对沙眼衣原体感染的敏感性低于野生型CHO细胞。缺乏硫酸乙酰肝素2- o磺化的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，EBs对宿主细胞的感染是由于EB表面对肝素具有亲和力的配体分子与宿主细胞表面的硫酸肝素蛋白聚糖受体特异性结合所致。这种结合可能取决于宿主细胞的硫酸肝素链，它是6- o -硫酸化的，比十二糖长。2-ODS肝素寡糖可能是预防沙眼衣原体感染的潜在药物。

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.