The Francisella pathogenicity island protein PdpD is required for full virulence and associates with homologues of the type VI secretion system

The Francisella pathogenicity island protein PdpD is required for full virulence and associates with homologues of the type VI secretion system
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DOI:
10.1128/jb.00198-08
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发表时间:
2008-07-01
影响因子:
3.2
通讯作者:
Nano, Francis E.
Nano, Francis E.
中科院分区:
生物学3区
文献类型:
--
作者:
Ludu, Jagjit S.;de Bruin, Olle M.;Nano, Francis E.

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图拉氏方济氏菌是一种高度传染性的兼性胞内细菌,是图拉热症的病原体。近一个世纪前,研究人员观察到,图拉热症在北美通常是致命的,但在欧洲和亚洲几乎从未致命。图拉氏F菌的染色体携带两个完全相同的弗朗西塞氏菌致病岛(FPI)副本,而北美特有生物型的FPI包含两个基因amnK和pdpD,这两个基因在整个北半球的生物型中没有找到。在这项工作中,我们研究了anmK和pdpD对毒力的贡献,它与图拉氏杆菌关系密切,但只携带一个fpI拷贝。我们证明了anmK和pdpD是完全毒力所必需的,但不是细胞内生长所必需的。这与迄今为止研究过的大多数其他FPI基因形成了鲜明对比,这些基因是细胞内生长所必需的。我们还发现PdpD定位于外膜。此外,PdpD的过度表达会影响FPI编码蛋白Igia、IgIB和Igic的细胞分布。最后,删除编码VI型分泌系统已知成分的同源蛋白的FPI基因,消除了IgIC分布的改变和PdpD的外膜定位。
Francisella tularensis is a highly infectious, facultative intracellular bacterial pathogen that is the causative agent of tularemia. Nearly a century ago, researchers observed that tularemia was often fatal in North America but almost never fatal in Europe and Asia. The chromosomes of F. tularensis strains carry two identical copies of the Francisella pathogenicity island (FPI), and the FPIs of North America-specific biotypes contain two genes, amnK and pdpD, that are not found in biotypes that are distributed over the entire Northern Hemisphere. In this work, we studied the contribution of anmK and pdpD to virulence by using F. novicida, which is very closely related to F. tularensis but which carries only one copy of the FPI. We showed that anmK and pdpD are necessary for full virulence but not for intracellular growth. This is in sharp contrast to most other FPI genes that have been studied to date, which are required for intracellular growth. We also showed that PdpD is localized to the outer membrane. Further, overexpression of PdpD affects the cellular distribution of FPI-encoded proteins IgIA, IgIB, and IgIC. Finally, deletions of FPI genes encoding proteins that are homologues of known components of type VI secretion systems abolished the altered distribution of IgIC and the outer membrane localization of PdpD.