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Role of Transferrin Receptor from a Neisseria meningitidis tbpB Isotype II Strain in Human Transferrin Binding and Virulence

机译:脑膜炎奈瑟氏菌tbpB同型II株的转铁蛋白受体在人转铁蛋白结合和毒力中的作用。

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Neisseria meningitidis acquires iron through the action of the transferrin (Tf) receptor, which is composed of the Tf-binding proteins A and B (TbpA and TbpB). Meningococci can be classified into isotype I and II strains depending on whether they harbor a type I or II form of TbpB. Both types of TbpB have been shown to differ in their genomic, biochemical, and antigenic properties. Here we present a comparative study of isogenic mutants deficient in either or both Tbps from the isotype I strain B16B6 and isotype II strain M982. We show that TbpA is essential in both strains for iron uptake and growth with iron-loaded human Tf as a sole iron source. No growth has also been observed for the TbpB? mutant of strain B16B6, as shown previously, whereas the growth of the analogous mutant in M982 was similar to that in the wild type. This indicates that TbpB in the latter strain plays a facilitating but not essential role in iron uptake, which has been observed previously in similar studies of other bacteria. These data are discussed in relation to the fact that isotype II strains represent more than 80% of serogroup B meningococcal strains. The contribution of both subunits in the bacterial virulence of strain M982 has been assessed in a murine model of bacteremia. Both the TbpB? TbpA? mutant and the TbpA? mutant are shown to be nonvirulent in mice, whereas the virulence of the TbpB? mutant is similar to that of the wild type.
机译:脑膜炎奈瑟氏球菌(Neisseria meningitidis)通过运铁蛋白(Tf)受体的作用获取铁,该受体由Tf结合蛋白A和B(TbpA和TbpB)组成。脑膜炎球菌可根据其是否携带TbpB的I型或II型分为I型和II型同种菌株。已显示两种类型的TbpB在基因组,生化和抗原特性方面均不同。在这里,我们提出了同基因突变体的比较研究,这些同基因突变体来自同型I株B16B6和同型II株M982的任一或两个Tbps均不足。我们表明,TbpA在铁吸收和铁载人Tf作为唯一铁源的生长中都至关重要。如前所述,菌株B16B6的TbpB β突变体也未观察到生长,而M982中类似突变体的生长与野生型相似。这表明后一种菌株中的TbpB在铁摄取中起促进作用,但不是必需的作用,这在先前对其他细菌的类似研究中已经观察到。这些数据是关于同型II菌株占B组血清脑膜炎球菌80%以上的事实进行讨论的。已经在鼠菌血症的鼠模型中评估了两个亚基在菌株M982的细菌毒力中的贡献。 TbpB ? TbpA ?突变体和TbpA ?突变体在小鼠中均无毒力,而TbpB 的毒力?突变体与野生型相似。

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