IglG and IglI of the Francisella Pathogenicity Island Are Important Virulence Determinants of Francisella tularensis LVS
IglG and IglI of the Francisella Pathogenicity Island Are Important Virulence Determinants of Francisella tularensis LVS
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DOI：
10.1128/iai.01344-10
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发表时间：
2011-09-01
影响因子：
3.1
通讯作者：
Sjostedt, Anders
中科院分区：
文献类型：
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作者：
Broms, Jeanette E.;Lavander, Moa;Sjostedt, Anders
革兰氏阴性菌土拉热弗朗西丝菌是土拉菌病的病原体，土拉菌病是一种与宿主巨噬细胞内细菌增殖密切相关的疾病。这反过来又需要表达弗朗西斯菌致病岛（FPI）基因，据信编码VI型分泌系统。虽然许多组分的确切功能尚未被揭示，但已发现一些组分有助于弗朗西斯菌引起小鼠全身感染的能力以及防止吞噬溶酶体融合和促进逃逸到宿主细胞质中。在到达该隔室后，细菌迅速繁殖，抑制炎性小体的活化，并最终导致宿主细胞的凋亡。在这项研究中，我们分析了FPI编码的蛋白IglG，IglI和PdpE对F.土拉菌在所有研究的测定中，Delta pdpE突变体的表现与亲本菌株相似。相反，Δ iglG和Δ iglI突变体，尽管它们在J774A中有效复制。1细胞，两者都表现出延迟的吞噬体逃逸，赋予延迟激活的炎性小体，并表现出降低的细胞致病性以及在小鼠模型中的显着衰减。因此，IglG和IglI在调节胞内宿主反应和F.土拉热。
The Gram-negative bacterium Francisella tularensis is the causative agent of tularemia, a disease intimately associated with the multiplication of the bacterium within host macrophages. This in turn requires the expression of Francisella pathogenicity island (FPI) genes, believed to encode a type VI secretion system. While the exact functions of many of the components have yet to be revealed, some have been found to contribute to the ability of Francisella to cause systemic infection in mice as well as to prevent phagolysosomal fusion and facilitate escape into the host cytosol. Upon reaching this compartment, the bacterium rapidly multiplies, inhibits activation of the inflammasome, and ultimately causes apoptosis of the host cell. In this study, we analyzed the contribution of the FPI-encoded proteins IglG, IglI, and PdpE to the aforementioned processes in F. tularensis LVS. The Delta pdpE mutant behaved similarly to the parental strain in all investigated assays. In contrast, Delta iglG and Delta iglI mutants, although they were efficiently replicating in J774A. 1 cells, both exhibited delayed phagosomal escape, conferred a delayed activation of the inflammasome, and exhibited reduced cytopathogenicity as well as marked attenuation in the mouse model. Thus, IglG and IglI play key roles for modulation of the intracellular host response and also for the virulence of F. tularensis.