Natural-host animal models indicate functional interchangeability between the filamentous haemagglutinins of Bordetella pertussis and Bordetella bronchiseptica and reveal a role for the mature C-terminal domain, but not the RGD motif, during infection.

Natural-host animal models indicate functional interchangeability between the filamentous haemagglutinins of Bordetella pertussis and Bordetella bronchiseptica and reveal a role for the mature C-terminal domain, but not the RGD motif, during infection.
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DOI:
10.1111/j.1365-2958.2009.06623.x
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发表时间:
2009-03
影响因子:
3.6
通讯作者:
Cotter PA
Cotter PA
中科院分区:
生物学2区
文献类型:
--
作者:
Julio SM;Inatsuka CS;Mazar J;Dieterich C;Relman DA;Cotter PA

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博德特氏菌属的细菌会导致呼吸道感染。广泛的宿主范围(例如支气管败血波氏杆菌)和人类适应(例如百日咳波氏杆菌)菌株都产生一种表面暴露和分泌的蛋白质,称为丝状血凝素(FHA),其在粘附和免疫调节中发挥作用。先前使用B的研究。百日咳和培养的哺乳动物细胞鉴定了几个在宿主细胞相互作用中具有潜在作用的FHA结构域,包括Arg-Gly-Asp(RGD)三联体,据报道其结合上皮细胞和单核细胞上的整联蛋白以激活宿主信号传导途径。我们在这里表明,与我们以前的报告相反,fha B基因的B。百日咳和B.支气管败血症是功能上可互换的,至少就所研究的各种体外和体内测定而言。该结果是重要的,因为它表明使用B研究FHA获得的信息。支气管败血症和自然宿主动物模型应适用于B。百日咳FHA也是如此。我们还表明,成熟FHA的C-末端,我们命名为MCD,介导粘附上皮细胞和巨噬细胞样细胞,是所需的大鼠呼吸道的殖民化和调节小鼠肺部的炎症反应。然而,我们无法检测到RGD在任何这些过程中的作用。
Bacteria of the Bordetella genus cause respiratory tract infections. Both broad host range (e.g. Bordetella bronchiseptica) and human-adapted (e.g. Bordetella pertussis) strains produce a surface-exposed and secreted protein called filamentous haemagglutinin (FHA) that functions in adherence and immunomodulation. Previous studies using B. pertussis and cultured mammalian cells identified several FHA domains with potential roles in host cell interactions, including an Arg-Gly-Asp (RGD) triplet that was reported to bind integrins on epithelial cells and monocytes to activate host signalling pathways. We show here that, in contrast to our previous report, the fhaB genes of B. pertussis and B. bronchiseptica are functionally interchangeable, at least with regard to the various in vitro and in vivo assays investigated. This result is significant because it indicates that information obtained studying FHA using B. bronchiseptica and natural-host animal models should apply to B. pertussis FHA as well. We also show that the C-terminus of mature FHA, which we name the MCD, mediates adherence to epithelial and macrophage-like cells and is required for colonization of the rat respiratory tract and modulation of the inflammatory response in mouse lungs. We could not, however, detect a role for the RGD in any of these processes.
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