CBRN Defence and Security, FOI Swedish Defence Research Agency, 901 82 Umeå, Sweden.
BMC Microbiol. 2010 Aug 26;10:227. doi: 10.1186/1471-2180-10-227.
All four Francisella tularensis subspecies possess gene clusters with potential to express type IV pili (Tfp). These clusters include putative pilin genes, as well as pilB, pilC and pilQ, required for secretion and assembly of Tfp. A hallmark of Tfp is the ability to retract the pilus upon surface contact, a property mediated by the ATPase PilT. Interestingly, out of the two major human pathogenic subspecies only the highly virulent type A strains have a functional pilT gene.
In a previous study, we were able to show that one pilin gene, pilA, was essential for virulence of a type B strain in a mouse infection model. In this work we have examined the role of several Tfp genes in the virulence of the pathogenic type A strain SCHU S4. pilA, pilC, pilQ, and pilT were mutated by in-frame deletion mutagenesis. Interestingly, when mice were infected with a mixture of each mutant strain and the wild-type strain, the pilA, pilC and pilQ mutants were out-competed, while the pilT mutant was equally competitive as the wild-type.
This suggests that expression and surface localisation of PilA contribute to virulence in the highly virulent type A strain, while PilT was dispensable for virulence in the mouse infection model.
所有四个弗朗西斯氏菌亚种都拥有具有表达 IV 型菌毛(Tfp)潜力的基因簇。这些簇包括推定的菌毛基因,以及 pilB、pilC 和 pilQ,它们是 Tfp 分泌和组装所必需的。Tfp 的一个标志是在表面接触时能够缩回菌毛,这一特性由 ATPase PilT 介导。有趣的是,在两种主要的人类致病亚种中,只有高毒力的 A 型菌株具有功能正常的 pilT 基因。
在之前的研究中,我们能够证明,在小鼠感染模型中,一个菌毛基因 pilA 对于 B 型菌株的毒力是必需的。在这项工作中,我们研究了几个 Tfp 基因在致病性 A 型菌株 SCHU S4 毒力中的作用。通过框内缺失诱变,pilA、pilC、pilQ 和 pilT 被突变。有趣的是,当用每种突变株和野生型株的混合物感染小鼠时,pilA、pilC 和 pilQ 突变株被竞争淘汰,而 pilT 突变株与野生型株同样具有竞争力。
这表明 PilA 的表达和表面定位有助于高毒力 A 型菌株的毒力,而 PilT 在小鼠感染模型中对毒力是可有可无的。