Characterization of a candidate Borrelia burgdorferi beta sub(3)-chain integrin ligand identified using a phage display library

The spirochaetal agents of Lyme disease, Borrelia burgdorferi (sensu lato) bind to integrins alpha sub(IIb) beta sub(3), alpha sub(v) beta sub(3) and alpha sub(5) beta sub(1) in purified form and on the surfaces of human cells. Using a phage display library of B. burgdorferi (sensu stricto) DNA, a candidate ligand for beta sub(3)-chain integrins was identified. The native B. burgdorferi protein, termed p66, is known to be recognized by human Lyme disease patient sera and to be expressed on the surface of the spirochaete. We show here that recombinant p66 binds specifically to beta sub(3)-chain integrins and inhibits attachment of intact B. burgdorferi to the same integrins. When expressed on the surface of Escherichia coli, this protein increases the attachment of E. coli to a transfected cell line that expresses alpha sub(v) beta sub(3), but not to the parental cell line, which expresses no beta sub(3)-chain integrins. Localization of p66 on the surface of B. burgdorferi, the ability of recombinant forms of the protein to bind to beta sub(3)-chain integrins and the fact that p66 and B. burgdorferi bind to beta sub(3)-chain integrins in a mutually exclusive manner make p66 an attractive candidate bacterial ligand for integrins alpha sub(IIb) beta sub(3) and alpha sub(v) beta sub(3).