Different classes of proteoglycans contribute to the attachment of Borrelia burgdorferi to cultured endothelial and brain cells.
The Lyme disease spirochete, Borrelia burgdorferi, infects multiple tissues, such as the heart, joint, skin, and nervous system and has been shown to recognize heparan sulfate and dermatan sulfate proteoglycans. In this study, we examined the contribution of different classes of proteoglycans to the attachment of the infectious B. burgdorferi strain N40 to several immortalized cell lines and primary cultured cells, including endothelial cells and brain cells. Bacterial attachment was inhibited by exogenous proteoglycans or by treatment of host cells with inhibitors of proteoglycan synthesis or sulfation, indicating that proteoglycans play a critical role in bacterial binding to diverse cell types. Binding to primary bovine capillary endothelial cells or a human endothelial cell line was also inhibited by digestion with heparinase or heparitinase but not with chondroitinase ABC. In contrast, binding to glial cell-enriched brain cell cultures or to a neuronal cell line was inhibited by all three lyases. Binding of strain N40 to immobilized heparin could be completely inhibited by dermatan sulfate, and conversely, binding to dermatan sulfate could be completely blocked by heparin. As measured by 50% inhibitory dose, heparin was a better inhibitor of binding than dermatan sulfate, regardless of whether the substrate was heparin or dermatan sulfate. These results are consistent with the hypotheses that the species of proteoglycans recognized by B. burgdorferi vary with cell type and that bacterial recognition of different proteoglycans is mediated by the same bacterial molecule(s).
Leong
J M
JM
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester 01655, USA. john.leong@banyan.ummed.edu
Wang
H
H
Magoun
L
L
Field
J A
JA
Morrissey
P E
PE
Robbins
D
D
Tatro
J B
JB
Coburn
J
J
Parveen
N
N
D000818:Animals; D001422:Bacterial Adhesion; D015748:Borrelia burgdorferi Group / Q000502:physiology*; D001921:Brain / Q000382:microbiology*; D002417:Cattle; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003871:Dermatan Sulfate / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000382:microbiology*; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D011509:Proteoglycans / Q000502:physiology*; D014709:Vero Cells
D003871:Dermatan Sulfate; D006497:Heparan Sulfate; D011509:Proteoglycans