Characterization of a candidate Borrelia burgdorferi beta3-chain integrin ligand identified using a phage display library.
The spirochaetal agents of Lyme disease, Borrelia burgdorferi (sensu lato) bind to integrins alphaIIbbeta3, alphavbeta3 and alpha5beta1 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 beta3-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 beta3-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 alphavbeta3, but not to the parental cell line, which expresses no beta3-chain integrins. Localization of p66 on the surface of B. burgdorferi, the ability of recombinant forms of the protein to bind to beta3-chain integrins and the fact that p66 and B. burgdorferi bind to beta3-chain integrins in a mutually exclusive manner make p66 an attractive candidate bacterial ligand for integrins alphaIIbbeta3 and alphavbeta3.
Coburn
J
J
Division of Rheumatology and Immunology, Tufts-New England Medical Center, Box 406, 750 Washington St., Boston, MA 02111, USA. jcoburn_bor@opal.tufts.edu
Chege
W
W
Magoun
L
L
Bodary
S C
SC
Leong
J M
JM
D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins; D015748:Borrelia burgdorferi Group / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins; D006801:Humans; D039661:Integrin beta3; D008024:Ligands; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; D019151:Peptide Library; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018272:Porins / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D039661:Integrin beta3; D008024:Ligands; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; C107893:Oms66 protein, Borrelia; D019151:Peptide Library; D010980:Platelet Membrane Glycoproteins; D018272:Porins; D011993:Recombinant Fusion Proteins; C461599:maltose transport system, E coli