Identification of a type IV secretion substrate of Brucella abortus that participates in the early stages of intracellular survival.

Identification of a type IV secretion substrate of Brucella abortus that participates in the early stages of intracellular survival.
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参与细胞内生存早期的布鲁氏菌流产的IV型分泌底物的鉴定。

DOI:
10.1111/cmi.12224
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发表时间:
2014-03
影响因子:
3.4
通讯作者:
Ugalde JE
Ugalde JE
中科院分区:
生物学2区
文献类型:
--
作者:
Döhmer PH;Valguarnera E;Czibener C;Ugalde JE

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流产布鲁氏菌是牛布鲁氏菌病的病原体,是一种细胞内病原体,其毒力完全依赖于 IV 型分泌系统。该分泌系统将效应蛋白转移到宿主细胞中,以调节细菌的细胞内命运,以便在其积极复制时建立一个安全的生态位。尽管在了解这种分泌系统如何参与毒力过程方面已经做了很多工作,但迄今为止还很少鉴定出效应蛋白。我们在此描述了仅存在于布鲁氏菌属中的 IV 型分泌底物 (SepA) 的鉴定。并且与已知蛋白质没有可检测到的同源性。该蛋白以 virB 依赖性方式在涉及周质中间体的两步过程中分泌,并且分泌对其功能是必需的。缺失突变体在专业和非专业吞噬细胞的细胞内复制的早期阶段表现出缺陷,尽管它比野生型亲本菌株更有效地侵入细胞。我们的结果表明,尽管突变体更具侵袭性,但它在排除溶酶体标记 Lamp-1 方面存在缺陷,并且在细胞内生命周期的早期阶段更有效地失活。
Brucella abortus, the etiological agent of bovine brucellosis, is an intracellular pathogen whose virulence is completely dependent on a type IV secretion system. This secretion system translocates effector proteins into the host cell to modulate the intracellular fate of the bacterium in order to establish a secure niche were it actively replicates. Although much has been done in understanding how this secretion system participates in the virulence process, few effector proteins have been identified to date. We describe here the identification of a type IV secretion substrate (SepA) that is only present in Brucella spp. and has no detectable homology to known proteins. This protein is secreted in a virB dependent manner in a two-step process involving a periplasmic intermediate and secretion is necessary for its function. The deletion mutant showed a defect in the early stages of intracellular replication in professional and non-professional phagocytes although it invades the cells more efficiently than the wild type parental strain. Our results indicate that, even though the mutant was more invasive, it had a defect in excluding the lysosomal marker Lamp-1 and was inactivated more efficiently during the early phases of the intracellular life cycle.
DOI: 10.1371/journal.pone.0035394
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期刊: PloS one
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影响因子: --
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