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中间链球菌纤维连接蛋白结合蛋白 FbpI 的特性与致病性研究。

Characterization and pathogenicity of fibronectin binding protein FbpI of Streptococcus intermedius.

机构信息

Division of Molecular Microbiology, Department of Microbiology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan.

出版信息

Arch Microbiol. 2020 Oct;202(8):2071-2081. doi: 10.1007/s00203-020-01922-y. Epub 2020 Jun 1.

DOI:10.1007/s00203-020-01922-y
PMID:32488560
Abstract

Streptococcus intermedius is a causative agent of brain or liver abscesses. S. intermedius produces intermedilysin that plays a pivotal role in pathogenicity. We identified other pathogenic factors and described a fibronectin binding protein (FBP) homolog of S. intermedius (FbpI) that mediated bacterial adhesion to epithelial cells and virulence for mice. The amino acid sequence of FbpI is similar to that of atypical FBPs, which do not possess a conventional secretion signal and an anchoring motif. A full-length recombinant FbpI (rFbpI) bound to immobilized fibronectin in a dose-dependent manner. The fibronectin binding activity of an N-terminal construct of rFbpI comprising the translation initiation methionine of the open reading frame to lysine 265 (rFbpI-N) bound immobilized fibronectin to a much lesser extent compared with rFbpI. A construct comprising the C-terminal domain (alanine 266 to methionine 549; rFbpI-C) bound immobilized fibronectin equivalently to rFbpI. Adherence of the isogenic mutant ΔfbpI to cultured epithelial cells and immobilized fibronectin was significantly lower than that of the wild-type strain. Abscess formation of ΔfbpI reduced in a mouse infection model compared with that in the wild-type. Thus, FbpI may play a role in bacterial adhesion to host cells and represent a critical pathogenic factor of S. intermedius.

摘要

中间链球菌是脑脓肿和肝脓肿的病原体。中间链球菌产生的中介溶素在致病性中起着关键作用。我们鉴定了其他致病因子,并描述了中间链球菌的纤维连接蛋白结合蛋白(FBP)同源物(FbpI),它介导细菌对上皮细胞的黏附以及对小鼠的毒力。FbpI 的氨基酸序列与不具有常规分泌信号和锚定基序的非典型 FBPs 相似。全长重组 FbpI(rFbpI)以剂量依赖的方式与固定化纤维连接蛋白结合。rFbpI-N(包含开放阅读框的起始甲硫氨酸到赖氨酸 265 的 N 端构建体)的纤维连接蛋白结合活性与 rFbpI 相比,与固定化纤维连接蛋白的结合程度要小得多。包含 C 末端结构域(丙氨酸 266 至蛋氨酸 549;rFbpI-C)的构建体与 rFbpI 相当程度地结合固定化纤维连接蛋白。与野生型菌株相比,同源缺失突变株 ΔfbpI 对培养上皮细胞和固定化纤维连接蛋白的黏附明显降低。与野生型相比,在小鼠感染模型中,ΔfbpI 脓肿形成减少。因此,FbpI 可能在细菌与宿主细胞的黏附中起作用,并代表中间链球菌的一个关键致病因子。

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