1 2 3 4 Legionella pneumophila translocated translation inhibitors are required for bacterial-5 induced host cell cycle arrest 2 3 2 Abstract 3 3The cell cycle machinery controls diverse cellular pathways and is tightly regulated. 4Misregulation of cell division plays a central role in the pathogenesis of many disease processes. 3 5 Various microbial pathogens interfere with the cell cycle machinery to promote host cell 3 6 colonization. Although cell cycle modulation is a common theme among pathogens, the role that 3 7 this interference plays in promoting diseases is unclear. Previously we demonstrated that the G 1 3 8 and G 2 /M phases of the host cell cycle are permissive for Legionella pneumophila replication, 3 9 while S phase provides a toxic environment for bacterial replication. In this study we show that 4 0 L. pneumophila avoids host S phase by blocking host DNA synthesis and preventing cell cycle 4 1 progression into S phase. Cell cycle arrest upon Legionella contact is dependent on the Icm/Dot 4 2 secretion system. In particular, we found that cell cycle arrest is dependent on the intact 4 3 enzymatic activity of translocated substrates that inhibits host translation. Moreover, we show 4 4 that early in infection, the presence of these translation inhibitors is crucial to induce the 4 5 degradation of the master regulator cyclin D1. Our results demonstrate that the bacterial effectors 4 6 that inhibit translation are associated with preventing entry of host cells into a phase associated 4 7 with restriction of L. pneumophila. Furthermore, control of cyclin D1 may be a common 4 8 strategy used by intracellular pathogens to manipulate the host cell cycle and promote bacterial 4 9
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.