Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
Cell Host Microbe. 2011 Jul 21;10(1):9-20. doi: 10.1016/j.chom.2011.06.003.
Several pathogenic bacteria utilize type III secretion systems (TTSS) to deliver into host cells bacterial virulence proteins with the capacity to modulate a variety of cellular pathways. Once delivered into host cells, the accurate targeting of bacterial effectors to specific locations is critical for their proper function. However, little is known about the mechanisms these virulence effectors use to reach their subcellular destination. Here we show that the Salmonella TTSS effector proteins SspH2 and SseI are localized to the plasma membrane of host cells, a process dependent on S-palmitoylation of a conserved cysteine residue within their N-terminal domains. We also show that effector protein lipidation is mediated by a specific subset of host-cell palmitoyltransferases and that lipidation is critical for effector function. This study describes a remarkable mechanism by which a pathogen exploits host-cell machinery to properly target its virulence factors.
几种致病性细菌利用 III 型分泌系统（TTSS）将具有调节多种细胞途径能力的细菌毒力蛋白输送到宿主细胞中。一旦输送到宿主细胞中，细菌效应物准确靶向特定位置对于其正常功能至关重要。然而，对于这些毒力效应物用于到达其亚细胞靶标的机制知之甚少。在这里，我们表明沙门氏菌 TTSS 效应蛋白 SspH2 和 SseI 定位于宿主细胞的质膜上，该过程依赖于其 N 端结构域内保守半胱氨酸残基的 S-棕榈酰化。我们还表明，效应蛋白的脂质化是由宿主细胞棕榈酰转移酶的特定亚群介导的，并且脂质化对于效应物功能至关重要。这项研究描述了一种病原体利用宿主细胞机制来正确靶向其毒力因子的惊人机制。
