Chlamydia-dependent biosynthesis of a heparan sulphate-like compound in eukaryotic cells

Abstract

SummaryOne hypothesis for the mechanism of chlamydial interaction with its eukaryotic host cell invokes a trimolecular mechanism, whereby a Chlamydia-derived glycosaminoglycan bridges a chlamydial acceptor molecule and a host receptor enabling attachment and invasion. We show that a heparan sulphate-speci®c monoclonal antibody speci®cally binds a glycosaminoglycan localized to the surface of the chlamydial organism and effectively neutralizes infectivity of both C. trachomatis and C. pneumoniae. In addition to the ability of this antibody to neutralize infectivity, direct visualization using immuno¯uorescence demonstrated staining of chlamydial organisms localized to the intracellular vacuole. The chlamydial-associated glycosaminoglycan was speci®cally labelled with [ 14 C]-glucosamine, and the labelled compound was immunoprecipitated and resolved by gel electrophoresis. The chlamydial-associated glycosaminoglycan is a high-molecular-weight compound similar in size to heparin or heparan sulphate and was sensitive to cleavage by heparan sulphate lyase. These data demonstrate that a glucosamine-containing sulphated polysaccharide is produced within the intracellular vacuole containing chlamydiae and is a target for antibody-mediated neutralization of infectivity.

Interaction of Chlamydia trachomatis with Mammalian Cells Is Independent of Host Cell Surface Heparan Sulfate Glycosaminoglycans

“…Chlamydiae are capable of binding heparan sulfate, and, consequently, the presence of heparan sulfate on the surfaces of host cells might be expected to affect adherence (2,5,12,26). This interaction is further complicated by data from several laboratories showing that chlamydial EB display heparan sulfate or a functionally analogous compound on their surfaces prior to infection (2,4,8,18,25,26). Moreover, it has recently been shown that fibronectin is also sequestered to the surfaces of EB as a natural outcome of in vitro infection and that fibronectin binding to EB is mediated by heparan sulfate lyase-sensitive components (13).…”

“…twofold) in susceptibility to chlamydial infection were observed for heparan sulfate-deficient CHO-761 cells (26). Larger reductions were observed for CHO-677 and CHO-745 cells (four-to eightfold); nevertheless, like the parental cell line CHO-K1, each cell line can readily be Ͼ90% infected using static inoculation (18). It was concluded that the reductions in infectivity for these CHO cell mutants were less than would be expected with the loss of a host cell surface molecule essential for the infection process.…”

Is Endothelial Nitric Oxide Synthase a Moonlighting Protein Whose Day Job is Cholesterol Sulfate Synthesis? Implications for Cholesterol Transport, Diabetes and Cardiovascular Disease

“…The most common such agent is Chlamydia pneumoniae [154,155]. Chlamydia pneumoniae can only grow and survive inside a host cell, where it accumulates in vacuolae and produces a glycosaminoglycan which bears an extremely strong resemblance to heparan sulfate [156]. We hypothesize that C. pneumoniae may be playing a protective role in providing heparan sulfate to the vasculature.…”

Is Encephalopathy a Mechanism to Renew Sulfate in Autism?

“…Chlamydia is especially significant for our arguments, as it has been demonstrated in in vitro studies that Chlamydia is capable of producing a type of polysaccharide that is almost indistinguishable from heparan sulfate [176]. High concentrations of this polysaccharide were detected specifically in intracellular vacuoles harboring Chlamydia, in three strains of eukaryotic cells that were impaired in different ways in their ability to produce heparan sulfate.…”