Inhibition of the PtdIns(5) kinase PIKfyve disrupts intracellular replication of Salmonella
- 18 March 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 29 (8), 1331-1347
- https://doi.org/10.1038/emboj.2010.28
Abstract
3‐phosphorylated phosphoinositides (3‐PtdIns) orchestrate endocytic trafficking pathways exploited by intracellular pathogens such as Salmonella to gain entry into the cell. To infect the host, Salmonellae subvert its normal macropinocytic activity, manipulating the process to generate an intracellular replicative niche. Disruption of the PtdIns(5) kinase, PIKfyve, be it by interfering mutant, siRNA‐mediated knockdown or pharmacological means, inhibits the intracellular replication of Salmonella enterica serovar typhimurium in epithelial cells. Monitoring the dynamics of macropinocytosis by time‐lapse 3D (4D) videomicroscopy revealed a new and essential role for PI(3,5)P2 in macropinosome‐late endosome/lysosome fusion, which is distinct from that of the small GTPase Rab7. This PI(3,5)P2‐dependent step is required for the proper maturation of the Salmonella ‐containing vacuole (SCV) through the formation of Salmonella ‐induced filaments (SIFs) and for the engagement of the Salmonella pathogenicity island 2‐encoded type 3 secretion system (SPI2‐T3SS). Finally, although inhibition of PIKfyve in macrophages did inhibit Salmonella replication, it also appears to disrupt the macrophage's bactericidal response. There is a [Have you seen ...?][1] (April 2010) associated with this Article. [1]: http://dx.doi.org/10.1038/emboj.2010.41Keywords
This publication has 64 references indexed in Scilit:
- Kinesin Adapter JLP Links PIKfyve to Microtubule-based Endosome-to-Trans-Golgi Network Traffic of FurinJournal of Biological Chemistry, 2009
- A protein complex that regulates PtdIns(3,5)P2 levelsThe EMBO Journal, 2009
- A role for SNX5 in the regulation of macropinocytosisBMC Cell Biology, 2008
- Function and dysfunction of the PI system in membrane traffickingThe EMBO Journal, 2008
- SopB promotes phosphatidylinositol 3-phosphate formation on Salmonella vacuoles by recruiting Rab5 and Vps34The Journal of cell biology, 2008
- PIKfyve: Partners, significance, debates and paradoxesCell Biology International, 2008
- A selective PIKfyve inhibitor blocks PtdIns(3,5)P2 production and disrupts endomembrane transport and retroviral buddingEMBO Reports, 2008
- Salmonella Trafficking is Defined by Continuous Dynamic Interactions with the Endolysosomal SystemTraffic, 2006
- The mammalian phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde transportJournal of Cell Science, 2006
- Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cellsThe EMBO Journal, 2000