title: Variable small protein (Vsp)-dependent and Vsp-independent pathways for glycosaminoglycan recognition by relapsing fever spirochaetes.
abstract: Tick-borne relapsing fever, caused by pathogenic Borrelia such as B. hermsii and B. turicatae, features recurrent episodes of bacteraemia, each of which is caused by a population of spirochaetes that expresses a different variable 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 immobilized heparin, and heparin and dermatan sulphate blocked bacterial binding to host cells. Bacterial binding was diminished by inhibition of host cell GAG synthesis or sulphation, or by the enzymatic removal of GAGs. GAGs mediated the attachment of relapsing fever spirochaetes to potentially relevant target cells, such as endothelial and glial cells. B. hermsii was able to attach to GAGs independently of variable major proteins, because strains expressing the variable major proteins Vsp33, Vlp7 or no variable major protein at all each recognized GAGs. Nevertheless, we found that a variable major 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. turicatae Oz1 serotype A, which expresses VspA. Recombinant VspB, but not VspA, bound to heparin and dermatan sulphate. Previous studies have shown that strain Oz1 serotype B grows to higher concentrations in the blood than does Oz1 serotype A. Thus, relapsing fever spirochaetes have the potential to express Vsp-dependent and Vsp-independent GAG-binding activities and, for one pair of highly related B. turicatae strains, differences in GAG binding correlate with differences in tissue tropism.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
authors.forename: L
authors.initials: L
authors.lastname: Magoun
authors.forename: W R
authors.initials: WR
authors.lastname: Zückert
authors.forename: D
authors.initials: D
authors.lastname: Robbins
authors.forename: N
authors.initials: N
authors.lastname: Parveen
authors.forename: K R
authors.initials: KR
authors.lastname: Alugupalli
authors.forename: T G
authors.initials: TG
authors.lastname: Schwan
authors.forename: A G
authors.initials: AG
authors.lastname: Barbour
authors.forename: J M
authors.initials: JM
authors.lastname: Leong
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001898:Borrelia / Q000378:metabolism* / Q000502:physiology; D016466:CHO Cells; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000378:metabolism; D006224:Cricetinae; D006025:Glycosaminoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012061:Relapsing Fever / Q000382:microbiology; D014407:Tumor Cells, Cultured
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D006025:Glycosaminoglycans; D011993:Recombinant Fusion Proteins; C121437:Vsp protein, bacterial; D006493:Heparin; D002809:Chondroitin Sulfates