Variable small protein (Vsp)-dependent and Vsp-independent pathways for glycosaminoglycan recognition by relapsing fever spirochaetes

Tick-borne relapsing fever, caused by pathogenic Borrelia such as B. hermsi i and B. turicatae, features recurrent episodes of bacteraemia, each of whi ch is caused by a population of spirochaetes that expresses a different var iable major protein. Relapsing fever is also associated with the infection of a variety of tissues, such as the central nervous system. In this study, we show that glycosaminoglycans (GAGs) mediate the attachment of relapsing fever spirochaetes to mammalian cells. B. hermsii strain DAH bound to immo bilized heparin, and heparin and dermatan sulphate blocked bacterial bindin g to host cells. Bacterial binding was diminished by inhibition of host cel l GAG synthesis or sulphation, or by the enzymatic removal of GAGs. GAGs me diated the attachment of relapsing fever spirochaetes to potentially releva nt target cells, such as endothelial and glial cells. B. hermsii was able t o attach to GAGs independently of variable major proteins, because strains expressing the variable major proteins Vsp33,,Vlp7 or no variable major pro tein at all each recognized GAGs. Nevertheless, we found that a variable ma jor protein of B. turicatae directly promoted GAG binding by this relapsing fever spirochaete. B. turicatae strain Oz1 serotype B, which expresses the variable major protein VspB, bound to GAGs more efficiently than did B. tu ricatae Oz1 serotype A, which expresses VspA, Recombinant VspB, but not Vsp A, bound to heparin and dermatan sulphate. Previous studies have shown that strain Oz1 serotype B grows to higher concentrations in the blood than doe s Oz1 serotype A. Thus, relapsing fever spirochaetes have the potential to express Vsp-dependent and Vsp-independent GAG-binding activities and, for o ne pair of highly related B. turicatae strains, differences in GAG binding correlate with differences in tissue tropism.