Key Points
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Bacterial pathogens exploit a range of niches within their hosts. A small number of bacteria, including Listeria monocytogenes, Shigella flexneri, Burkholderia pseudomallei, Francisella tularensis and Rickettsia spp., are able to gain access to and proliferate in the cell cytosol and are termed cytosolic bacteria.
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Escape from the vacuole following invasion is crucial for cytosolic pathogens. Bacteria escape rapidly from the vacuole through mechanisms that rely on the production of secreted enzymes and form pores to disrupt the vacuolar membrane. Interestingly, with the exception of F. tularensis, all cytosolic bacteria use actin-based motility after entry into the cytosol and spread to neighbouring cells.
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Little is known about the biochemical composition of the mammalian cell cytosol and a key, but unresolved, question is whether the cytosol is permissive for bacterial growth.
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Cytosolic bacteria are adapted to replicate in the cell cytosol. Studies identifying the bacterial genes and growth requirements that are important for intracellular replication have been informative regarding the nutrient availability within the cytosol. The cytosol seems to be limiting for compounds such as aromatic amino acids, and bacteria can readily use carbon sources, including pyruvate (by Rickettsia spp.) and hexose phosphates (by S. flexneri and L. monocytogenes), that must be available to microorganisms in the cytosol.
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Bacteria in the cytosol are recognized by the innate immune system and autophagy is a key component of the host defence against cytosolic bacteria. There is increasing evidence that cytosolic bacteria interact and modify the autophagic pathway to promote their survival.
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Cytosolic bacteria have evolved several mechanisms to adapt to their preferred niche. Future work on these pathogens will provide information on the cytosol as a site for replication and the bacterial strategies required to survive within it. Furthermore, it is becoming appreciated that a wider range of bacteria can exploit this host niche during steps in their pathogenesis.
Abstract
Bacterial pathogens exploit a huge range of niches within their hosts. Many pathogens can invade non-phagocytic cells and survive within a membrane-bound compartment. However, only a small number of bacteria, including Listeria monocytogenes, Shigella flexneri, Burkholderia pseudomallei, Francisella tularensis and Rickettsia spp., can gain access to and proliferate within the host cell cytosol. Here, we discuss the mechanisms by which these cytosolic pathogens escape into the cytosol, obtain nutrients to replicate and subvert host immune responses.
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Acknowledgements
This work was supported by the European Initiative for Basic Research in Microbiology and Infectious Diseases grant D005-P09205 funded by the Commission of the European Communities (to K.R.) and by the Fondation pour la Recherche Médicale (to B.M.).
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Salmonella enterica subspecies enterica serovar Typhimurium
FURTHER INFORMATION
Glossary
- Trigger mechanism
-
A mechanism used by bacteria, such as the genera Shigella and Salmonella, to enter cells. Bacteria interact directly with the eukaryotic cell cytoskeleton by injecting bacterial effectors through a dedicated secretion system. These effectors cause massive cytoskeletal rearrangements to engulf the bacterium in an entry vacuole.
- Zipper mechanism
-
A mechanism used by bacteria, such as the genera Yersinia or Listeria, to enter cells. Bacteria contact and adhere to the eukaryotic cell through the binding of a bacterial surface protein to a eukaryotic surface receptor, often a transmembrane cell-adhesion protein. Modest membrane extensions and cytoskeletal rearrangements engulf the bacterium in an entry vacuole.
- Vacuole
-
A single-membrane organelle within the cell cytosol that encloses a fluid-filled compartment.
- Phagolysosome
-
A membrane-enclosed organelle formed by the fusion of a lysosome, which is an organelle containing hydrolytic enzymes, and a phagosome, which is a membranous vacuole formed around a particle.
- Lysosome
-
A membrane-bound organelle that contains hydrolytic enzymes.
- Microbicidal
-
An activity that is lethal for microorganisms.
- Listeriolysin O
-
(LLO). A thiol-activated cholesterol-dependent pore-forming toxin produced by Listeria monocytogenes. The production of LLO is essential for escape of the bacterium from the vacuole into the cytosol during invasion, and therefore LLO is a key virulence factor.
- Type C phospholipase
-
A subclass of enzymes that cleave the polar head group of phosphoinositides between the glycerol and phosphate moieties.
- Thiol reductase
-
An enzyme that catalyses disulphide bond reduction.
- Type III secretion system
-
A secretion apparatus of Gram-negative bacteria that allows bacterial effector proteins to be delivered directly into the eukaryotic cell cytosol through a bacterial molecular needle complex.
- Oxidoreductase
-
A class of enzymes that catalyse oxidoreduction reactions which transfer electrons from a hydrogen donor to a hydrogen acceptor.
- Disulphide bond
-
A single covalent bond formed from the coupling of two thiol groups, the functional group of which is composed of a sulphur and a hydrogen atom.
- Glutathione
-
A tripeptide that acts as an antioxidant and electron donor in the cell cytosol by reducing disulphide bonds formed between cysteines of cytoplasmic proteins.
- Ferritin
-
A globular protein that consists of 24 subunits and is the main intracellular iron storage protein in eukaryotes.
- Auxotrophic
-
The state of an organism when it is unable to synthesize a particular organic compound required for growth.
- Diaminopimelate
-
The ionic form of the amino acid diaminopimelic acid, which is a compound found in the peptidoglycan of bacteria.
- Oxygen tension
-
The partial pressure of oxygen.
- Complement
-
A crucial part of the innate immune system that consists of enzyme cascades which lead to bacterial lysis and promote phagocytosis.
- Antimicrobial peptide
-
A conserved component of the innate immune system that consists of polypeptides, with fewer than 100 amino acid residues, that have the ability to kill microorganisms.
- Pathogen-associated molecular pattern
-
A small molecular motif that is consistently found on pathogens and is recognized as a non-self molecule by a pattern recognition receptor of the innate immune system.
- Nod-like receptor
-
One of a family of proteins that serve as pattern recognition receptors, in that they sense microbial motifs in the cell cytoplasm.
- Autophagy
-
A degradative pathway by which cytosolic content, organelles and pathogens are delivered to lysosomes as part of cellular homeostasis and innate immunity.
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Ray, K., Marteyn, B., Sansonetti, P. et al. Life on the inside: the intracellular lifestyle of cytosolic bacteria. Nat Rev Microbiol 7, 333–340 (2009). https://doi.org/10.1038/nrmicro2112
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DOI: https://doi.org/10.1038/nrmicro2112
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