Chlamydia-dependent biosynthesis of a heparan sulphate-like compound in eukaryotic cells.
One 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-specific monoclonal antibody specifically binds a glycosa-minoglycan 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 immunofluorescence demonstrated staining of chlamydial organisms localized to the intracellular vacuole. The chlamydial-associated glycosaminoglycan was specifically labelled with [14C]-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.
Rasmussen-Lathrop
S J
SJ
The Francis I. Proctor Foundation, University of California, San Francisco 94143, USA.
Koshiyama
K
K
Phillips
N
N
Stephens
R S
RS
D000818:Animals; D016466:CHO Cells; D002689:Chlamydia / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D002690:Chlamydia Infections / Q000382:microbiology; D006224:Cricetinae; D005057:Eukaryotic Cells / Q000382:microbiology*; D005455:Fluorescent Antibody Technique; D006025:Glycosaminoglycans / Q000235:genetics / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D009500:Neutralization Tests; D011233:Precipitin Tests
D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D008024:Ligands