Decorin‐binding adhesins from Borrelia burgdorferi

Abstract

SummaryLyme disease is a tick-transmitted infection caused by the spirochete Borrelia burgdorferi. Ticks deposit B. burgdorferi into the dermis of the host, where they eventually become associated with collagen fibres. We demonstrated previously that B. burgdorferi is unable to bind collagen, but can bind the collagenassociated proteoglycan decorin and expresses decorin-binding proteins (Dbps). We have now cloned and sequenced two genes encoding the proteins, DbpA and DbpB, which have a similar structure, as revealed by circular dichroism (CD) spectroscopy of recombinant proteins. Competition experiments revealed a difference in binding specificity between DbpA and DbpB. Western blot analysis of proteinase K-treated intact B. burgdorferi and transmission electron microscopy studies using antibodies raised against recombinant Dbps demonstrated that these proteins are surface exposed. DbpA effectively inhibits the attachment of B. burgdorferi to a decorin substrate, whereas DbpB had a marginal effect, suggesting a difference in substrate specificity between the two Dbps. Polystyrene beads coated with DbpA adhered to a decorincontaining extracellular matrix produced by cultured skin fibroblasts, whereas beads coated with OspC did not. Taken together, these data suggest that Dbps are adhesins of the MSCRAMM (microbial surface component-recognizing adhesive matrix molecule) family, which mediate B. burgdorferi attachment to the extracellular matrix of the host.

Overexpression of CsrA (BB0184) Alters the Morphology and Antigen Profiles ofBorrelia burgdorferi

“…6D) and DbpA (Fig. 6E), which are well-characterized adhesins mediating adherence of B. burgdorferi to fibronectin (64,75) and decorin (39), respectively. In addition, there was increased expression of BBA64 in ES25 while there was little or no expression of this lp54-encoded protein in both the parental control strain and MSK5 when these strains are propagated in BSK-II medium at pH 7.6 and 32°C.…”

“…Differential gene expression plays a critical role in the transmission, colonization, and dissemination of B. burgdorferi in mammalian hosts. Several of these open reading frames (ORFs) include mediators that provide a selective advantage to B. burgdorferi by enhancing its ability to adhere to host matrices (24,39,64) and to evade the mediators of innate and adaptive immunity (16,26,48,89), as well as other deleterious physiological processes encountered in its hosts (27). A number of studies have determined the significance of alterations of surface lipoproteins in response to these signals, and the molecular mechanisms responsible for these changes are beginning to be understood (41,86).…”

Identification and Characterization of the C3 Binding Domain of the Staphylococcus aureus Extracellular Fibrinogen-binding Protein (Efb)

“…The recombinant proteins rEfb (17), rEfb104, rEfb120, and rEfb165 were expressed as recombinant N-terminal His-tagged proteins that allowed for purification using metal ion-chelating chromatography as described previously (12,59). Proteins were expressed and purified as previously described (59,60).…”

Biology of Infection with Borrelia burgdorferi

“…Among the B. burgdorferi proteins that bind ECM components are DbpA and DbpB, which bind decorin [145], BBK32, which binds fibronectin [146], Bgp, which binds proteoglycans [147], and P66, which binds integrins [148]. These proteins may help B. burgdorferi migrate through mammalian tissue and persist in joints and skin, where the spirochetes may be inaccessible to circulating antibodies.…”