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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.

沙眼衣原体（C.沙眼衣原体）血清型L2感染的真核宿主细胞使用组织培养模型感染系统进行研究。观察到有效的抑制感染性时，基本体（EBs）暴露于肝素或当HeLa 229细胞用肝素酶处理。相反，未观察到显著抑制。当EB暴露于由IdoA-GlcNS（6S）的重复二糖单元组成的化学2-O-去甲酰基肝素（2-ODS肝素）时，观察到相同的有效抑制，但当暴露于分别由IdoA（2S）-GlcNS或IdoA-GlcNS的重复二糖单元组成的化学6-O-去甲酰基肝素（6-ODS肝素）或完全去甲酰基化和N-再硫酸化肝素（CDSNS肝素）时，观察不到相同的有效抑制。2-ODS肝素的抑制作用可以观察到其寡糖长于十二糖。突变的CHO细胞系677缺乏硫酸乙酰肝素的生物合成，对C.沙眼衣原体感染的CHO细胞。缺乏硫酸乙酰肝素2-O-硫酸化的F-17细胞对感染具有与野生型CHO细胞相同的敏感性。这些数据表明EB感染宿主细胞是由于EB表面上对肝素具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，其是6-O-硫酸化的并且比十二糖长。2-ODS肝素寡糖可能是一种潜在的预防C.沙眼感染