Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Infect Immun. 2018 Aug 22;86(9). doi: 10.1128/IAI.00318-18. Print 2018 Sep.
Virulence of in mammals requires the type III secretion system, which delivers seven effector proteins into the cytoplasm of host cells to undermine immune responses. All seven of these effectors are conserved across strains, but three, YopJ, YopT, and YpkA, are apparently dispensable for virulence. Some degree of functional redundancy between effector proteins would explain both observations. Here, we use a combinatorial genetic approach to define the minimal subset of effectors required for full virulence in mice following subcutaneous infection. We found that a strain lacking YopJ, YopT, and YpkA is attenuated for virulence in mice and that addition of any one of these effectors to this strain increases lethality significantly. YopJ, YopT, and YpkA likely contribute to virulence via distinct mechanisms. YopJ is uniquely able to cause macrophage cell death and to suppress accumulation of inflammatory cells to foci of bacterial growth in deep tissue, whereas YopT and YpkA cannot. The synthetic phenotypes that emerge when YopJ, YopT, and YpkA are removed in combination provide evidence that each effector enhances virulence and that YopT and YpkA act through a mechanism distinct from that of YopJ.
在哺乳动物中，毒力需要 III 型分泌系统，该系统将七种效应蛋白输送到宿主细胞的细胞质中，以破坏免疫反应。这七种效应蛋白在 菌株中都保守，但 YopJ、YopT 和 YpkA 三种显然对毒力是可有可无的。效应蛋白之间存在一定程度的功能冗余可以解释这两种观察结果。在这里，我们使用组合遗传方法来定义在皮下感染后导致小鼠完全毒力所需的最小效应子子集。我们发现，缺乏 YopJ、YopT 和 YpkA 的 菌株在小鼠中的毒力减弱，并且向该菌株中添加这些效应子中的任何一种都会显著增加致死率。YopJ、YopT 和 YpkA 可能通过不同的机制导致毒力。YopJ 是唯一能够导致巨噬细胞死亡并抑制炎症细胞在深部组织中细菌生长焦点处聚集的效应子，而 YopT 和 YpkA 则不能。当 YopJ、YopT 和 YpkA 同时被去除时出现的综合表型提供了证据，表明每个效应子都增强了 毒力，并且 YopT 和 YpkA 通过与 YopJ 不同的机制发挥作用。
