title: Borrelia burgdorferi RevA antigen binds host fibronectin.
abstract: Borrelia burgdorferi, the Lyme disease-causing spirochete, can persistently infect its vertebrate hosts for years. B. burgdorferi is often found associated with host connective tissue, where it interacts with components of the extracellular matrix, including fibronectin. Some years ago, a borrelial surface protein, named BBK32, was identified as a fibronectin-binding protein. However, B. burgdorferi BBK32 mutants are still able to bind fibronectin, indicating that the spirochete possesses additional mechanisms for adherence to fibronectin. We now demonstrate that RevA, an unrelated B. burgdorferi outer surface protein, binds mammalian fibronectin in a saturable manner. Site-directed mutagenesis studies identified the amino terminus of the RevA protein as being required for adhesion to fibronectin. RevA bound to the amino-terminal region of fibronectin. RevA binding to fibronectin was not inhibited by salt or heparin, suggesting that adhesin-ligand interactions are primarily nonionic and occur through the non-heparin-binding regions of the fibronectin amino-terminal domains. revA genes are widely distributed among Lyme disease spirochetes, and the present studies determined that all RevA alleles tested bound fibronectin. In addition, RevB, a paralogous protein found in a subset of B. burgdorferi strains, also bound fibronectin. We also confirmed that RevA is produced during mammalian infection but not during colonization of vector ticks and determined that revA transcription is controlled through a mechanism distinct from that of BBK32.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Chandler Medical Center MN469, Lexington, Kentucky 40536-0298, USA. catherine.brissette@uky.edu
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Brissette
authors.forename: Tomasz
authors.initials: T
authors.lastname: Bykowski
authors.forename: Anne E
authors.initials: AE
authors.lastname: Cooley
authors.forename: Amy
authors.initials: A
authors.lastname: Bowman
authors.forename: Brian
authors.initials: B
authors.lastname: Stevenson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000502:physiology; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D018884:Ixodes / Q000382:microbiology; D008193:Lyme Disease / Q000382:microbiology; D051379:Mice / Q000382:microbiology; D008807:Mice, Inbred BALB C / Q000382:microbiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D016415:Sequence Alignment
chemical_list: D001425:Bacterial Outer Membrane Proteins; D005353:Fibronectins; C434447:RevA protein, Borrelia burgdorferi