Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan.
Pharmaceutical Department, Shujitsu University, Okayama, Japan.
Microbiol Immunol. 2021 Aug;65(8):333-341. doi: 10.1111/1348-0421.12917. Epub 2021 Jul 16.
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 -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 (III ), 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 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 (rIII ) 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 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.
纤连蛋白（Fn）是一种大约 450kDa 的糖蛋白，由 12 个 I 型、2 个 II 型和 15-17 个 III 型模块组成。Fn 的纤化对于组织重建和伤口愈合很重要。我们之前报道过产气荚膜梭菌产生几种 Fn 结合蛋白（Fbps），其中两种，FbpA 和 FbpB，与 III-C（Fn 的一个片段，来源于第一个 III 型模块的羧基末端三分之二）结合。真皮蛋白（DPT），一种 22kDa 的非胶原细胞外基质蛋白，可加速正常胶原纤化并诱导 Fn 纤化。DPT 与 Fn III 型（III ）相互作用，导致 Fn 构象发生变化，并促进 Fn 纤化。在这里，我们研究了 FbpA 和 FbpB 对 Fn 和 III 片段与 DPT 的结合以及 DPT 诱导的 Fn 纤化的影响。重组 FbpA（rFbpA）和重组 FbpB（rFbpB）均显著抑制 Fn 与 DPT 和重组 III（rIII）的结合，抑制 DPT 诱导的 Fn 纤化。此外，发现 rFbpA 和 rFbpB 均能显著结合包被的 DPT，在酶联亲和素生物素复合物系统中，而 rIII 既不能结合包被的 rFbpA 也不能结合包被的 rFbpB。总之，FbpA 和 FbpB 通过与 DPT 的相互作用抑制 DPT 诱导的 Fn 纤化。伤口和/或感染组织中从裂解的产气荚膜梭菌细胞中释放的 FbpA 和 FbpB 可能会阻止 Fn 纤化并延迟伤口愈合过程，从而使感染恶化。
