Legionella pneumophila is an intracellular pathogen that requires nutrients from the host for its replication. It has been shown that replicating L. pneumophila prefers amino acids as main sources of carbon and energy. The homeostasis of amino acids in eukaryotic cells is regulated by the transcription factor EB (TFEB), which translocates into the nucleus and activates genes for autophagy and lysosomal biogenesis. Here we show that the Legionella effector SetA causes a robust nuclear translocation of TFEB when exogenously expressed in mammalian cells and that the translocation is dependent on the glucosyltransferase activity of SetA. We further show that SetA directly glucosylates TFEB at multiple sites. Our findings of TFEB glucosylation by SetA may suggest an alternative strategy for exploiting host nutrients in addition to the control of host mTORC1 signaling by L. pneumophila. Our results provide further insight into the molecular mechanism of the delicate TFEB nuclear shuttling.

肺炎军团菌是一种细胞内病原体，需要宿主提供营养才能进行复制。业已表明，复制肺炎链球菌偏爱氨基酸作为碳和能量的主要来源。真核细胞中氨基酸的稳态由转录因子EB（TFEB）调节，该因子易位进入细胞核并激活自噬和溶酶体生物发生的基因。这里我们展示军团菌当在哺乳动物细胞中外源表达时，效应子SetA引起TFEB的强健的核易位，并且该易位依赖于SetA的葡糖基转移酶活性。我们进一步表明，SetA在多个位点直接糖基化TFEB。我们通过SetA对TFEB进行糖基化的研究结果可能提出了利用宿主营养物质的另一种策略，除了通过嗜肺乳杆菌控制宿主mTORC1信号传递。我们的研究结果提供了对精细的TFEB核穿梭分子机制的进一步了解。