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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2
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The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2

机译:病原体相关的iroA基因簇介导lipocalin 2的细菌逃逸。

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Numerous bacteria cope with the scarcity of iron in their microenvironment by synthesizing small iron-scavenging molecules known as siderophores. Mammals have evolved countermeasures to block siderophore-mediated iron acquisition as part of their innate immune response. Secreted lipocalin 2 (Lcn2) sequesters the Escherichia coli siderophore enterobactin (Ent), preventing E. coli from acquiring iron and protecting mammals from infection by E. coli. Here, we show that the iroA gene cluster, found in many pathogenic strains of Gram-negative enteric bacteria, including E. coli, Salmonella spp., and Klebsiella pneumoniae, allows bacteria to evade sequestration of Ent by Lcn2. We demonstrate that C-glucosylated derivatives of Ent produced by iroA-encoded enzymes do not bind purified Lcn2, and an iroA-harboring strain of E. coli is insensitive to the growth inhibitory effects of Lcn2 in vitro. Furthermore, we show that mice rapidly succumb to infection by an iroA-harboring strain of E. coli but not its wild-type counterpart, and that this increased virulence depends on evasion of host Lcn2. Our findings indicate that the iroA gene cluster allows bacteria to evade this component of the innate immune system, rejuvenating their Ent-mediated iron-acquisition pathway and playing an important role in their virulence.
机译:许多细菌通过合成小的铁清除分子(称为铁载体)来解决其微环境中铁的缺乏问题。哺乳动物已经发展出对策,以阻止铁载体介导的铁的获得,作为其先天免疫反应的一部分。分泌的lipocalin 2(Lcn2)隔离大肠埃希菌铁载体肠杆菌素(Ent),从而阻止大肠杆菌获得铁并保护哺乳动物免受大肠杆菌感染。在这里,我们表明,在革兰氏阴性肠杆菌的许多致病菌株(包括大肠杆菌,沙门氏菌和肺炎克雷伯菌)中发现的iroA基因簇,使细菌能够逃避Lcn2对Ent的螯合。我们证明,由iroA编码的酶产生的Ent的C-葡萄糖基化衍生物不结合纯化的Lcn2,而具有iroA的大肠杆菌菌株对Lcn2的体外生长抑制作用不敏感。此外,我们显示小鼠迅速屈服于感染有iroA的大肠杆菌,但没有野生型对应物,而且这种增加的毒力取决于逃避宿主Lcn2。我们的发现表明,iroA基因簇使细菌能够逃避先天免疫系统的这一组成部分,使它们的Ent介导的铁获取途径恢复活力,并在其毒力中发挥重要作用。

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