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

The spirochaetal agents of Lyme disease, Borrelia burgdorferi (sensu lato) bind to integrins alpha(IIb)beta(3), alpha(v)beta(3), and alpha(5)beta(1) i n purified form and on the surfaces of human cells. Using a phage display l ibrary of B. burgdorferi (sensu stricto) DNA, a candidate ligand for beta(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 b e expressed on the surface of the spirochaete. We show here that recombinan t p66 binds specifically to beta(3)-chain integrins and inhibits attachment of intact B. burgdorferi to the same integrins. When expressed on the surf ace of Escherichia coli, this protein increases the attachment of E. coli t o a transfected cell line that expresses alpha(v)beta(3), but not to the pa rental cell line, which expresses no beta(3)-chain integrins. Localization of p66 on the surface of B. burgdorferi, the ability of recombinant forms o f the protein to bind to beta(3)-chain integrins and the fact that p68 and B. burgdorferi bind to beta(3)-chain integrins in a mutually exclusive mann er make p66 an attractive candidate bacterial ligand for integrins alpha(II b)beta(3) and alpha(v)beta(3).