Inhibition of the interaction between fibronectin and dermatopontin by Clostridium perfringens fibronectin‐binding proteins

Abstract Fibronectin (Fn) is an approximately 450 kDa glycoprotein that consists of 12 type I, 2 type II, and 15–17 type III modules. Fibrillation of Fn is important for tissue reconstitution and wound healing. We previously reported that Clostridium perfringens produces several Fn‐binding proteins (Fbps), two of which, FbpA and FbpB, bind to III 1 ‐C (a fragment of Fn derived from the carboxyl‐terminal two‐thirds of the first‐type III module). Dermatopontin (DPT), a 22 kDa noncollagenous extracellular matrix protein, accelerates normal collagen fibrillation and induces Fn fibrillation. DPT interacts with Fn‐type III 12–14 (III 12–14 ), leading to a change in Fn conformation and promoting Fn fibrillation. Here, we investigated the effects of FbpA and FbpB on the binding of Fn and the III 12–14 fragment to DPT and on the DPT‐induced Fn fibrillation. Both recombinant FbpA (rFbpA) and recombinant FbpB (rFbpB) significantly inhibited Fn binding to DPT and recombinant III 12–14 (rIII 12–14 ) binding, and inhibited DPT‐induced Fn fibrillation. Furthermore, it was found that both rFbpA and rFbpB significantly bound to coated DPT in an enzyme‐linked avidin–biotin complex system, whereas rIII 12–14 did not bind to either coated rFbpA or rFbpB. In conclusion, both FbpA and FbpB inhibited DPT‐induced Fn fibrillation via their interaction with DPT. Both FbpA and FbpB released from lysed C. perfringens cells in wounds and/or infected tissue may prevent Fn fibrillation and delay the wound healing process, subsequently exacerbating infection.