Abstract
SummaryLegionella 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.
Highlights
The gram-negative bacterium, Legionella pneumophila, is a facultative intracellular pathogen that parasitizes freshwater amoeba in nature (Fields, 1996)
DNA constructs from the library were than transfected into the transcription factor EB (TFEB)-GFP HeLa cells individually, and the intracellular localization of TFEB-GFP was analyzed by fluorescence microscopy
As a validation of our findings, two effectors that induced the nuclear translocation of TFEB, sdeA and sdeC, which encode enzymes that catalyze a unique type of phosphoribosyl ubiquitination independent of E1 or E2 enzymes (Bhogaraju et al, 2016; Kotewicz et al, 2017; Qiu et al, 2017), were reported to induce nuclear translocation of TFEB in a similar screen (De Leon et al, 2017)
Summary
The gram-negative bacterium, Legionella pneumophila, is a facultative intracellular pathogen that parasitizes freshwater amoeba in nature (Fields, 1996). L. pneumophila can replicate inside human alveolar macrophages upon the inhalation of bacteria-containing aerosols, causing a severe form of pneumonia known as Legionnaires’ disease (Fraser et al, 1977; Horwitz and Silverstein, 1980). Upon entry into host cells, L. pneumophila releases a repertoire of 300 effector proteins through the Dot/Icm type IV secretion system to establish a replication niche, known as the Legionella-containing vacuole (LCV) (Hubber and Roy, 2010; Qiu and Luo, 2017). Like other intracellular bacterial pathogens, L. pneumophila relies on energy and anabolic substrates derived from the nutrient-limited intracellular environment for propagation. Accumulative evidence has documented that L. pneumophila utilizes a variety of strategies to stimulate nutrient supply from the host for optimal growth and replication
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
