INTEGRINS ALPHA(V)BETA(3) AND ALPHA(5)BETA(1) MEDIATE ATTACHMENT OF LYME-DISEASE SPIROCHETES TO HUMAN-CELLS

Borrelia burgdorferi (sensu lato), the agent of Lyme disease, is able to cause chronic, multisystemic infections in human and animal hosts. Attachment of the spirochete to host cells is likely to be important f or the colonization of diverse tissues. The platelet-specific integrin alpha(IIb)beta(3) was previously identified as a receptor for all thr ee species of Lyme disease spirochetes (B. burgdorferi sensu stricto, B. garinii, and B. afzelii). Here we show that B. burgdorferi also rec ognizes the widely expressed integrins alpha(v) beta(3) and alpha(5) b eta(1), known as the vitronectin and fibronectin receptors, respective ly. Three representatives of each species of Lyme disease spirochete w ere tested for the ability to bind to purified alpha(v) beta(3) and al pha(5) beta(1). All of the strains tested bound to at least one integr in. Binding to one integrin was not always predictive of binding to ot her integrins, and several different integrin preference profiles were identified. Attachment of the infectious B. burgdorferi strain N40 to purified alpha(v) beta(3) and alpha(5) beta(1), was inhibited by RGD peptides and the appropriate receptor-specific antibodies. Binding to alpha(v) beta(3) was also shown by using a transfected cell line that expresses this receptor but not alpha(III)beta(3). Attachment of B. bu rgdorferi N40 to human erythroleukemia cells and to human saphenous ve in endothelial cells was mediated by both alpha(5) beta(1) and alpha(v ) beta(3). Our results show that multiple integrins mediate attachment of Lyme disease spirochetes to host cells.