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Type IV Pili in Francisella tularensis: Roles of pilF and pilT in Fiber Assembly, Host Cell Adherence, and Virulence

机译:图拉弗朗西斯菌中的IV型菌毛:pilF和pilT在纤维装配,宿主细胞粘附和毒力中的作用

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Francisella tularensis, a highly virulent facultative intracellular bacterium, is the causative agent of tularemia. Genome sequencing of all F. tularensis subspecies revealed the presence of genes that could encode type IV pili (Tfp). The live vaccine strain (LVS) expresses surface fibers resembling Tfp, but it was not established whether these fibers were indeed Tfp encoded by the pil genes. We show here that deletion of the pilF putative Tfp assembly ATPase in the LVS resulted in a complete loss of surface fibers. Disruption of the pilT putative disassembly ATPase also caused a complete loss of pili, indicating that pilT functions differently in F. tularensis than in model Tfp systems such as those found in Pseudomonas aeruginosa and Neisseria spp. The LVS pilF and pilT mutants were attenuated for virulence in a mouse model of tularemia by the intradermal route. Furthermore, although absence of pili had no effect on the ability of the LVS to replicate intracellularly, the pilF and pilT mutants were defective for adherence to macrophages, pneumocytes, and hepatocytes. This work confirms that the surface fibers expressed by the LVS are encoded by the pil genes and provides evidence that the Francisella pili contribute to host cell adhesion and virulence.
机译:图拉弗朗西斯菌是一种高毒性兼性细胞内细菌,是图拉菌血症的病原体。所有 F的基因组测序。 tularensis 亚种揭示了可以编码IV型菌毛(Tfp)的基因的存在。活疫苗株(LVS)表达类似于Tfp的表面纤维,但尚未确定这些纤维是否确实是 pil 基因编码的Tfp。我们在此处显示LVS中 pilF 假定的Tfp装配ATPase的缺失导致表面纤维的完全丧失。假定的 pilT 分解ATPase的破坏也导致菌毛的完全丧失,表明 pilT F中的功能有所不同。 tularensis 比Tfp模型系统(例如铜绿假单胞菌 Neisseria spp中发现的模型)要高。 LVS的 pilF pilT 突变体通过皮内途径减弱了鼠李糖血症小鼠模型的毒力。此外,尽管菌毛的缺乏对LVS在细胞内复制的能力没有影响,但 pilF pilT 突变体对于巨噬细胞,肺细胞和肝细胞的粘附是有缺陷的。这项工作证实了LVS表达的表面纤维是由 pil 基因编码的,并提供了 Francisella pili有助于宿主细胞粘附和致病力的证据。

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