Mechanism and inhibitors of Chlamydia trachomatis infection of eukaryotic host cells

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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.