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.

Borrelia burgdorferi cp32 BpaB Modulates Expression of the Prophage NucP Nuclease and SsbP Single-Stranded DNA-Binding Protein

“…The cp32 elements of Lyme disease spirochetes, such as B. burgdorferi, are of particular interest, since they encode Erp, RevA, and Mlp lipoproteins. These bacterial surface proteins are produced by the bacterium during mammalian infection, and those with known functions serve as adhesins for host components, such as plasmin(ogen), laminin, and complement factor H (1,7,8,9,10,13,22,25,26,32,33,38,42,43,49,63). Sequences of the erp, revA, and mlp loci generally vary between different cp32s (Fig.…”

Enhanced Adhesion and OspC Protein Synthesis of the Lyme Disease Spirochete Borrelia Burgdorferi Cultivated in a Host-Derived Tissue Co-Culture System

“…An examination of the paradigm for reciprocal regulation of ospA and ospC revealed that the heterogeneous expression of OspA and OspC by spirochete populations during the tick blood meal results from the intricate order of transcriptional and translational changes that ensue as B. burgdorferi transitions between the vector tick and mammalian host (8). Brisette et al found that also RevA is produced during mammalian infection but not during colonisation of vector ticks (9). A proteome study demonstrated that the response of B. burgdorferi to changing in vitro culture conditions.…”

Borrelia burgdorferi RevA Significantly Affects Pathogenicity and Host Response in the Mouse Model of Lyme Disease

“…The interactions of B. burgdorferi with fibronectin are facilitated by several distinct bacterial surface proteins, including BBK32, RevA, BB0347, and CspA (BbCRASP-1) (28)(29)(30)(31). The redundancy in adhesins makes it difficult to dissect the role of each B. burgdorferi fibronectin binding protein in the pathogenesis of Lyme disease.…”

“…RevA expression is elevated during mammalian infection over its expression in the tick vector, suggesting a role in pathogenesis (30,(34)(35)(36). RevA binds to fibronectin, and anti-RevA antibodies block the binding of whole B. burgdorferi bacteria to fibronectin (30).…”