Key Points
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Bacterial effector proteins have the ability to modulate a variety of host cell functions to promote bacterial survival and replication. In some cases, numerous effectors with diverse biochemical activities are delivered into host cells, and the spatial regulation of these activities is crucial for bacterial infection.
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Many bacterial effectors have evolved targeting mechanisms that use the host cell machinery. Some of these mechanisms use signal sequences embedded within the effector, and others require post-translational modification of the effector before subcellular targeting.
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Three well-characterized effector-targeting mechanisms are effector lipidation, effector ubiquitylation and effector binding to phospholipids. In addition, bacterial effectors can engage organelle import pathways to localize to specific organelles within the host cell.
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It is clear that, despite the unique subcellular organization within host cells, many bacterial effectors have evolved the ability to selectively target precise eukaryotic compartments by exploiting a variety of eukaryotic targeting mechanisms to ensure proper effector function during infection.
Abstract
Several bacterial species have evolved specialized secretion systems to deliver bacterial effector proteins into eukaryotic cells. These effectors have the capacity to modulate host cell pathways in order to promote bacterial survival and replication. The spatial and temporal context in which the effectors exert their biochemical activities is crucial for their function. To fully understand effector function in the context of infection, we need to understand the mechanisms that lead to the precise subcellular localization of effectors following their delivery into host cells. Recent studies have shown that bacterial effectors exploit host cell machinery to accurately target their biochemical activities within the host cell.
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Acknowledgements
Work in the J.E.G. laboratory on the subjects discussed in this article has been supported by US National Institutes of Health (NIH) grants AI055472 and AI079022 to J.E.G. S.W.H. was supported by a National Research Service Award fellowship from the NIH.
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Glossary
- Lipid rafts
-
Small (∼70 nm width), dynamic microdomains of the plasma membrane that are enriched in cholesterol, and in sphingolipids and phospholipids with saturated acyl chains.
- Caveolae
-
Specialized lipid raft regions of the plasma membrane that contain the protein caveolin and form flask-shaped, cholesterol-rich invaginations of the membrane.
- E3 ligase
-
An enzyme that is required to attach the molecular tag ubiquitin to proteins, This tag modifies protein function or targets the protein for proteosomal degradation.
- Caspases
-
A family of Cys-Asp proteases involved in apoptosis, necrosis and inflammasome activation.
- Legionella-containing vacuole
-
A host cell membrane-dervived compartment in which intracellular growth of Legionella spp. occurs.
- Salmonella-induced filaments
-
A tubular network of membranes that extend from the Salmonella-containing vacuole.
- ESCRT
-
(Endosomal sorting complex required for transport). A conserved cellular machinery for the sorting of ubiquitylated cargo proteins into vesicles and the subsequent scission of the membrane neck.
- Guanine nucleotide exchange factor
-
(GEF). A protein that induces a GTPase to exchange GTP for GDP, resulting in activation of the GTPase.
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Hicks, S., Galán, J. Exploitation of eukaryotic subcellular targeting mechanisms by bacterial effectors. Nat Rev Microbiol 11, 316–326 (2013). https://doi.org/10.1038/nrmicro3009
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DOI: https://doi.org/10.1038/nrmicro3009
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