Strain variation in glycosaminoglycan recognition influences cell-type-specific binding by Lyme disease spirochetes

Lyme disease, a chronic multisystemic disorder that can affect the skin, he art, joints, and nervous system is caused by Borrelia burgdorferi sensu lat o. Lyme disease spirochetes were previously shown to bind glycosaminoglycan s (GAGs). In the current study, the GAG-binding properties of eight Lyme di sease strains were determined. Binding by two high-passage HB19 derivatives to Vero cells could not be inhibited by enzymatic removal of GAGs or by th e addition of exogenous GAG. The other six strains, which included a differ ent high-passage HB19 derivative (HB19 clone 1), were shown to recognize bo th heparan sulfate and dermatan sulfate in cell-binding assays, but the rel ative efficiency of binding to these two GAGs varied among the strains. Str ains N40, CA20-2A, and PBi bound predominantly to heparan sulfate, PBo boun d both heparan sulfate and dermatan sulfate roughly equally, and VS461 and HB19 clone 1 recognized primarily dermatan sulfate. Cell binding by strain HB19 clone 1 was inhibited better by exogenous dermatan sulfate than by hep arin, whereas heparin was the better inhibitor of binding by strain N40. Th e GAG-binding preference of a Lyme disease strain was reflected in its cell -type-specific binding. Strains that recognized predominantly heparan sulfa te bound efficiently to both C6 glioma cells and EA-Hy926 cells, whereas st rains that recognized predominantly dermatan sulfate bound well only to the glial cells. The effect of lyase treatment of these cells on bacterial bin ding was consistent with the model that cell-type-specific binding was a re flection of the GAG-binding preference. We conclude that the GAG-binding pr eference varies with the strain of Lyme disease spirochete and that this va riation influences cell type-specific binding in vitro.